1 00:00:05,600 --> 00:00:08,280 WELCOME TO OUR SECOND DAY OF THE 2 00:00:08,280 --> 00:00:10,520 ICCVAM PUBLIC FORUM. 3 00:00:10,520 --> 00:00:12,480 GLAD TO SEE SMILING FACES HERE 4 00:00:12,480 --> 00:00:15,440 IN THE ROOM TODAY, HOPE ALL OF 5 00:00:15,440 --> 00:00:20,120 YOU HAVE YOUR CUP OF COFFEE AT 6 00:00:20,120 --> 00:00:20,680 HOME. 7 00:00:20,680 --> 00:00:23,120 TODAY WILL BE A NICE DAY, WE 8 00:00:23,120 --> 00:00:25,520 HAVE A BUNCH OF PUBLIC COMMENTS 9 00:00:25,520 --> 00:00:26,040 COMING IN. 10 00:00:26,040 --> 00:00:28,480 NICOLE WILL KICK US OFF WITH 11 00:00:28,480 --> 00:00:30,200 SUMMARY OF WRITTEN PUBLIC 12 00:00:30,200 --> 00:00:31,600 STATEMENTS AND SEVERAL PEOPLE IN 13 00:00:31,600 --> 00:00:33,040 THE AUDIENCE WITH PUBLIC 14 00:00:33,040 --> 00:00:35,600 COMMENTS TO COME IN, AND WE'LL 15 00:00:35,600 --> 00:00:44,040 HAVE SEVERAL TALKS FROM ICCVAM, 16 00:00:44,040 --> 00:00:44,520 NICEATM, DEPARTMENT OF 17 00:00:44,520 --> 00:00:45,440 AGRICULTURE, DEPARTMENT OF 18 00:00:45,440 --> 00:00:47,720 DEFENSE, NIH AND OTHERS WITH A 19 00:00:47,720 --> 00:00:48,840 QUESTION AND ANSWER PERIOD AT 20 00:00:48,840 --> 00:00:50,920 THE END. 21 00:00:50,920 --> 00:00:54,200 LET'S GET STARTED ON DAY 2. 22 00:00:54,200 --> 00:00:59,520 THANK YOU FOR COMING. 23 00:00:59,520 --> 00:01:00,680 >> THANK YOU, JOHN. 24 00:01:00,680 --> 00:01:03,760 SO, WE DO ALSO HAVE ADDITION TO 25 00:01:03,760 --> 00:01:04,680 AGENDA TODAY, WHERE OUR 26 00:01:04,680 --> 00:01:06,480 COLLEAGUE FROM THE V.A. OFFICE 27 00:01:06,480 --> 00:01:07,920 OF RESEARCH AND DEVELOPMENT WAS 28 00:01:07,920 --> 00:01:10,320 ABLE TO JOIN US TODAY, AND SO 29 00:01:10,320 --> 00:01:12,400 WE'RE STILL HAVING A COUPLE 30 00:01:12,400 --> 00:01:17,760 TECHNICAL ISSUES WITH THE ZOOM 31 00:01:17,760 --> 00:01:20,280 MEETING SO HE WILL -- I'M NOT 32 00:01:20,280 --> 00:01:25,120 SURE ANYONE HEARD YOU, JOHN, 33 00:01:25,120 --> 00:01:25,960 BECAUSE YOU WERE MUTED. 34 00:01:25,960 --> 00:01:28,800 WOULD YOU LIKE TO COME BACK UP 35 00:01:28,800 --> 00:01:31,160 AND WELCOME EVERYONE AGAIN? 36 00:01:31,160 --> 00:01:33,520 >> OKAY. 37 00:01:33,520 --> 00:01:37,360 38 00:01:37,360 --> 00:01:41,280 >> FOR THOSE OF YOU WHO ARE NOT 39 00:01:41,280 --> 00:01:43,680 LIPREADERS, SORRY ABOUT THAT. 40 00:01:43,680 --> 00:01:45,080 WELCOME TO DAY 2. 41 00:01:45,080 --> 00:01:46,680 A REALLY GOOD DAY, A BUNCH OF 42 00:01:46,680 --> 00:01:48,720 GOOD PUBLIC COMMENTS THAT ARE 43 00:01:48,720 --> 00:01:50,600 GOING TO BE DOWN HERE IN A 44 00:01:50,600 --> 00:01:51,840 COUPLE MINUTES, NICOLE WILL KICK 45 00:01:51,840 --> 00:01:54,240 US OFF WITH SUMMARY OF WRITTEN 46 00:01:54,240 --> 00:01:56,720 STATEMENT, SEVERAL PEOPLE IN THE 47 00:01:56,720 --> 00:01:58,600 ROOM WILL DO PUBLIC COMMENTS, 48 00:01:58,600 --> 00:01:59,920 SOME ONLINE AS WELL. 49 00:01:59,920 --> 00:02:05,800 AND SEVERAL TALKS FROM THE V.A., 50 00:02:05,800 --> 00:02:10,720 NICEATM, ICCVAM, DEPARTMENT OF 51 00:02:10,720 --> 00:02:12,040 AGRICULTURE, DoD, NIH, IF YOU 52 00:02:12,040 --> 00:02:13,600 HAVE QUESTIONS TOWARDS THE END 53 00:02:13,600 --> 00:02:14,600 LET US KNOW. 54 00:02:14,600 --> 00:02:20,160 AND HOPEFULLY YOU HEARD ME THIS 55 00:02:20,160 --> 00:02:20,360 TIME. 56 00:02:20,360 --> 00:02:20,680 >> OKAY. 57 00:02:20,680 --> 00:02:20,880 GREAT. 58 00:02:20,880 --> 00:02:21,720 THANKS, APPARENTLY IT WAS JUST 59 00:02:21,720 --> 00:02:24,880 THE ZOOM THAT WAS MUTED, THE 60 00:02:24,880 --> 00:02:27,480 WEBCAST WAS STILL OKAY. 61 00:02:27,480 --> 00:02:28,560 ALL RIGHT. 62 00:02:28,560 --> 00:02:29,400 SO, AS JOHN MENTIONED, OUR 63 00:02:29,400 --> 00:02:33,640 COLLEAGUE FROM THE V.A. OFFICE 64 00:02:33,640 --> 00:02:34,520 OF RESEARCH AND DEVELOPMENT WILL 65 00:02:34,520 --> 00:02:36,320 BE ABLE TO JOIN US TODAY, WE'LL 66 00:02:36,320 --> 00:02:38,120 DO THAT PRESENTATION LATER IN 67 00:02:38,120 --> 00:02:38,760 THE AGENDA. 68 00:02:38,760 --> 00:02:42,080 FIRST WE'LL START WITH OUR 69 00:02:42,080 --> 00:02:44,160 PUBLIC COMMENTS THAT WE'VE 70 00:02:44,160 --> 00:02:44,520 RECEIVED. 71 00:02:44,520 --> 00:02:46,320 I WILL DRAW YOUR ATTENTION TO 72 00:02:46,320 --> 00:02:47,520 THE WRITTEN PUBLIC COMMENTS THAT 73 00:02:47,520 --> 00:02:50,280 ARE AVAILABLE ON THE ICCVAM 74 00:02:50,280 --> 00:02:54,840 WEBSITE, SPECIFICALLY ON THE 75 00:02:54,840 --> 00:02:56,040 ICCVAM PUBLIC FORUM, THE SAME 76 00:02:56,040 --> 00:02:58,800 PLACE YOU REGISTERED FOR THE 77 00:02:58,800 --> 00:02:59,040 MEETING. 78 00:02:59,040 --> 00:02:59,880 THERE ARE PDFs AVAILABLE OF 79 00:02:59,880 --> 00:03:02,320 THE WRITTEN COMMENTS RECEIVED 80 00:03:02,320 --> 00:03:07,320 FROM THE PHYSICIANS COMMITTEE 81 00:03:07,320 --> 00:03:07,920 FOR RESPONSIBLE MEDICINE, 82 00:03:07,920 --> 00:03:09,920 CRUELTY FREE INTERNATIONAL AND 83 00:03:09,920 --> 00:03:12,800 HUMANE SOCIETY AND TWO OF THE 84 00:03:12,800 --> 00:03:14,120 THREE GROUPS ARE GIVING ORAL 85 00:03:14,120 --> 00:03:15,240 PUBLIC COMMENTS TODAY. 86 00:03:15,240 --> 00:03:16,760 I'M GOING TO KICK OFF THE ORAL 87 00:03:16,760 --> 00:03:20,400 PUBLIC STATEMENTS PORTION OF THE 88 00:03:20,400 --> 00:03:20,600 AGENDA. 89 00:03:20,600 --> 00:03:24,440 DO WE HAVE AMY KYLE ONLINE? 90 00:03:24,440 --> 00:03:26,080 OUR FIRST PUBLIC COMMENTER. 91 00:03:26,080 --> 00:03:30,720 IF NOT WE CAN CERTAINLY CIRCLE 92 00:03:30,720 --> 00:03:34,720 BACK AND -- OKAY. 93 00:03:34,720 --> 00:03:42,520 WE DO HAVE JESSE SALK FROM 94 00:03:42,520 --> 00:03:43,520 TWINSTRAND BIOSCIENCE ONLINE. 95 00:03:43,520 --> 00:03:46,440 WE'LL TURN IT OVER TO JESSE. 96 00:03:46,440 --> 00:03:48,760 THANK YOU FOR HAVING ME AND 97 00:03:48,760 --> 00:03:50,440 LETTING ME GIVE A COMMENT. 98 00:03:50,440 --> 00:03:54,200 I'M HERE AT 6 A.M. IN SEATTLE, 99 00:03:54,200 --> 00:03:55,480 SO HOPEFULLY THINGS ARE GOING 100 00:03:55,480 --> 00:03:57,840 WELL AT 9 A.M. ON THE EAST 101 00:03:57,840 --> 00:03:59,520 COAST. 102 00:03:59,520 --> 00:04:02,880 I'M GOING TO TALK ABOUT NEW 103 00:04:02,880 --> 00:04:05,960 TECHNOLOGY WE THINK IS GOING TO 104 00:04:05,960 --> 00:04:07,480 BE VERY SIGNIFICANT FOR THE 105 00:04:07,480 --> 00:04:08,880 FUTURE OF GENOMIC SAFETY 106 00:04:08,880 --> 00:04:10,120 TESTING, WANTED TO BRING THIS TO 107 00:04:10,120 --> 00:04:10,640 THE PUBLIC'S ATTENTION. 108 00:04:10,640 --> 00:04:11,720 THIS IS SOMETHING WE'VE BEEN 109 00:04:11,720 --> 00:04:16,960 WORKING ON WITH A VARIETY OF 110 00:04:16,960 --> 00:04:22,680 COLLABORATORS WHO ARE AT FDA, 111 00:04:22,680 --> 00:04:24,200 OTHER REGULATORY BODIES, HESSE 112 00:04:24,200 --> 00:04:25,120 AND WHAT NOT. 113 00:04:25,120 --> 00:04:27,760 THE BROAD CATEGORY OF TECHNOLOGY 114 00:04:27,760 --> 00:04:35,760 IS AIR CORRECTED SEQUENCING, NEW 115 00:04:35,760 --> 00:04:45,720 TOOLS THAT A ALLOW EXISTING DANK 116 00:04:45,720 --> 00:04:46,720 EXISTING DNA 117 00:04:46,720 --> 00:04:48,560 SEQUENCERS TO BE MORE ACCURATE 118 00:04:48,560 --> 00:04:50,120 TO USE GENOMIC SAFETY ASSAYS 119 00:04:50,120 --> 00:04:53,480 WHICH ARE SELECTION BASED IN 120 00:04:53,480 --> 00:04:55,760 ANIMALS OR BACTERIA TO 121 00:04:55,760 --> 00:04:57,320 POTENTIALLY BE REPLACED OR 122 00:04:57,320 --> 00:04:59,720 AUGMENTED USING DIRECT 123 00:04:59,720 --> 00:05:04,320 SEQUENCING OF DNA. 124 00:05:04,320 --> 00:05:05,960 I'M WITH TWINSTRAND BIOSCIENCE 125 00:05:05,960 --> 00:05:07,720 IN SEATTLE, TECHNOLOGY OUT OF 126 00:05:07,720 --> 00:05:12,080 THE UNIVERSITY OF WASHINGTON, 127 00:05:12,080 --> 00:05:12,960 DEVELOPED DUPLEX SEQUENCING, 128 00:05:12,960 --> 00:05:14,400 HIGH ACCURACY FORM OF AIR 129 00:05:14,400 --> 00:05:15,480 CORRECTED DNA SEQUENCING. 130 00:05:15,480 --> 00:05:18,040 THE WAY THIS WORKS WITHOUT GOING 131 00:05:18,040 --> 00:05:23,320 INTO ALL THE DETAILS IS THAT WE 132 00:05:23,320 --> 00:05:26,720 LABEL INDIVIDUAL DNA MOLECULES 133 00:05:26,720 --> 00:05:28,960 WITH SPECIAL MOLECULAR BARCODES 134 00:05:28,960 --> 00:05:31,320 THAT RECAPITULATE SOMETHING THAT 135 00:05:31,320 --> 00:05:34,480 HAPPENS IN NATURE, WHICH IS 136 00:05:34,480 --> 00:05:35,640 DURING CELL REPLICATION TO 137 00:05:35,640 --> 00:05:37,520 ENSURE HIGH FIDELITY OF COPYING 138 00:05:37,520 --> 00:05:38,440 OF CELLS. 139 00:05:38,440 --> 00:05:42,040 WE ESSENTIALLY ARE ABLE TO READ 140 00:05:42,040 --> 00:05:42,800 THE INDIVIDUAL -- THE SEQUENCES 141 00:05:42,800 --> 00:05:44,440 OF INDIVIDUAL STRANDS OF 142 00:05:44,440 --> 00:05:46,760 INDIVIDUAL MOLECULES AND COMPARE 143 00:05:46,760 --> 00:05:48,920 THE SEQUENCE TOGETHER AT THE END 144 00:05:48,920 --> 00:05:51,760 WHICH ALLOWS US TO ACHIEVE ERROR 145 00:05:51,760 --> 00:05:56,760 RATES BETWEEN LOW 1 IN 10 146 00:05:56,760 --> 00:05:58,000 MILLION. 147 00:05:58,000 --> 00:06:00,600 THIS REMOVES TRADITIONAL ERRORS, 148 00:06:00,600 --> 00:06:04,000 SEEN IN CONVENTIONAL DNA 149 00:06:04,000 --> 00:06:04,680 SEQUENCING. 150 00:06:04,680 --> 00:06:05,320 IT'S PREDOMINANTLY USED NOW 151 00:06:05,320 --> 00:06:09,160 WHICH HAS AN ERROR RATE OF 152 00:06:09,160 --> 00:06:10,800 AROUND 1%, THIS LETS YOU -- YOU 153 00:06:10,800 --> 00:06:16,360 CAN SEE AN EXAMPLE ON THE RIGHT 154 00:06:16,360 --> 00:06:18,560 STANDARD - LEFT STANDARD, ON THE 155 00:06:18,560 --> 00:06:19,840 RIGHT DUPLEX SEQUENCING, 156 00:06:19,840 --> 00:06:21,080 ESSENTIALLY ALL THE BACKGROUND 157 00:06:21,080 --> 00:06:22,920 NEWS WITH STANDARD GOES AWAY AND 158 00:06:22,920 --> 00:06:25,120 THERE'S ONE TRUE MUTATION HERE. 159 00:06:25,120 --> 00:06:28,760 THIS GIVES YOU A VISUAL TO 160 00:06:28,760 --> 00:06:29,280 UNDERSTANDING WHAT THIS 161 00:06:29,280 --> 00:06:30,560 TECHNOLOGY DOES. 162 00:06:30,560 --> 00:06:36,600 HOW IT CAN BE APPLIED IS RATHER 163 00:06:36,600 --> 00:06:39,360 THAN FOR MUTAGENESIS TESTING, 164 00:06:39,360 --> 00:06:41,000 EXAMPLE, RATHER THAN NEEDING TO 165 00:06:41,000 --> 00:06:44,200 TAKE BACTERIA OR CELLS OR 166 00:06:44,200 --> 00:06:46,560 ANIMALS THAT HAVE INTEGRATED 167 00:06:46,560 --> 00:06:49,680 REPORTERS THAT IF A MUTATION 168 00:06:49,680 --> 00:06:51,480 HAPPENS AND ALLOWS, YOU KNOW, A 169 00:06:51,480 --> 00:06:54,880 POPULATION OF CELLS TO GROW LIKE 170 00:06:54,880 --> 00:06:58,600 AIMS ASSAY AND CULTURE OR A 171 00:06:58,600 --> 00:06:59,600 PLAQUE, TRANSGENIC RODENT ASSAY 172 00:06:59,600 --> 00:07:02,000 WE'RE DIRECTLY ABLE TO SEQUENCE 173 00:07:02,000 --> 00:07:05,000 BILLIONS OF NUCLEOTIDES DIRECTLY 174 00:07:05,000 --> 00:07:06,360 FROM ANY TISSUE, ANY SPECIES, 175 00:07:06,360 --> 00:07:07,840 AND BASICALLY COUNT HOW MANY 176 00:07:07,840 --> 00:07:09,600 MUTATIONS THERE ARE IF WE 177 00:07:09,600 --> 00:07:11,320 SEQUENCE A BILLION NUCLEOSIDES 178 00:07:11,320 --> 00:07:16,280 THEN WE SEE, YOU KNOW, A HUNDRED 179 00:07:16,280 --> 00:07:17,600 MUTATIONS, MUTANT FREQUENCY IS 180 00:07:17,600 --> 00:07:19,800 100 DIVIDED BY A BILLION, THAT'S 181 00:07:19,800 --> 00:07:21,960 THE ORDER OF MAGNITUDE WE'RE 182 00:07:21,960 --> 00:07:24,360 TYPICALLY LOOKING AT. 183 00:07:24,360 --> 00:07:27,160 WE TAKE A REPRESENTATIVE PANEL, 184 00:07:27,160 --> 00:07:28,000 SEQUENCES ACROSS REPRESENTATIVE 185 00:07:28,000 --> 00:07:29,160 PORTION OF THE GENOME VARIABLE 186 00:07:29,160 --> 00:07:31,920 TO SEE ANY TYPE OF MUTATION, 187 00:07:31,920 --> 00:07:35,320 THIS ALLOWS US TO GET VERY 188 00:07:35,320 --> 00:07:39,040 QUANTITATIVE MUTANT FREQUENCY IN 189 00:07:39,040 --> 00:07:41,000 SPECTRA AND DETAILED 190 00:07:41,000 --> 00:07:43,200 TRINUCLEOTIDE SIGNATURES, VERY 191 00:07:43,200 --> 00:07:44,400 RELEVANT TO MUTATIONAL 192 00:07:44,400 --> 00:07:44,760 PROCESSES. 193 00:07:44,760 --> 00:07:47,240 AND ALLOWS US TO NOT ONLY DO 194 00:07:47,240 --> 00:07:50,640 THIS QUICKLY AND EFFICIENTLY 195 00:07:50,640 --> 00:07:51,840 WITHOUT ANY ENGINEERED SYSTEMS 196 00:07:51,840 --> 00:07:55,720 BUT IT CAN BE APPLIED BOTH IN 197 00:07:55,720 --> 00:07:57,640 VIVO AND IN VITRO. 198 00:07:57,640 --> 00:07:58,720 THE TECHNOLOGY IS BROADLY 199 00:07:58,720 --> 00:08:00,360 APPLICABLE TO DIFFERENT FORMS OF 200 00:08:00,360 --> 00:08:01,280 GENOMIC SAFETY. 201 00:08:01,280 --> 00:08:03,960 WE CAN APPLY TO CLASSIC 202 00:08:03,960 --> 00:08:06,920 MUTAGENESIS WHICH IS WHAT I'M 203 00:08:06,920 --> 00:08:11,080 MOSTLY TALKING ABOUT TODAY, CAN 204 00:08:11,080 --> 00:08:13,840 BE APPLIED TO CRISPR, NEW 205 00:08:13,840 --> 00:08:15,600 MODALITIES OF POTENTIAL MUTAGENS 206 00:08:15,600 --> 00:08:19,200 THAT CAN HAVE ALL-TARGET EFFECTS 207 00:08:19,200 --> 00:08:23,040 IN OTHER AREAS, MORE BROAD TO 208 00:08:23,040 --> 00:08:25,320 CARCINOGEN IS DETECTING 209 00:08:25,320 --> 00:08:25,840 NON-GENOTOXIC CARCINOGENS. 210 00:08:25,840 --> 00:08:28,280 WE DEVELOPED -- WE WORKED WITH 211 00:08:28,280 --> 00:08:30,880 PARTNERS AND CURE RATED LARGE 212 00:08:30,880 --> 00:08:33,880 AMOUNT OF EVIDENCE TO DATE 213 00:08:33,880 --> 00:08:36,840 BRIDGING STUDIES FROM PASS, 214 00:08:36,840 --> 00:08:40,000 STANDARD ASSAYS, TRANSGENIC 215 00:08:40,000 --> 00:08:41,920 RODENT, PIG-A, INTERLAB, 216 00:08:41,920 --> 00:08:43,960 REPRODUCIBILITY STUDIES, AROUND 217 00:08:43,960 --> 00:08:47,120 10 PUBLICATIONS, THAT HAVE BEEN 218 00:08:47,120 --> 00:08:50,400 PROGRESSIVELY MOVING ALONG FROM 219 00:08:50,400 --> 00:08:52,920 SHOWING EQUIVALENCY TO REALLY 220 00:08:52,920 --> 00:08:55,000 FOCUSING ON HOW WE CAN THINK 221 00:08:55,000 --> 00:08:56,400 BROADLY WHAT SPECIFICALLY IT 222 00:08:56,400 --> 00:08:58,240 WOULD TAKE TO APPLY THIS 223 00:08:58,240 --> 00:09:00,120 TECHNOLOGY IN A REGULATORY 224 00:09:00,120 --> 00:09:01,200 SETTING. 225 00:09:01,200 --> 00:09:02,960 WE WORK WITH HESSE CONSORTIUM, 226 00:09:02,960 --> 00:09:04,400 HAD A PUBLICATION THAT GROUP PUT 227 00:09:04,400 --> 00:09:15,080 OUT A FEW MONTHS AGO, A POSITION 228 00:09:15,080 --> 00:09:19,080 PAPER, SHOWING A FEW EXAMPLES 229 00:09:19,080 --> 00:09:21,560 HERE MUTANT FREE QUINCY, EXAMPLE 230 00:09:21,560 --> 00:09:23,000 OF BEING ABLE TO QUANTITATIVELY 231 00:09:23,000 --> 00:09:24,840 TAKE DNA OUT OF THE BONE MARROW 232 00:09:24,840 --> 00:09:29,800 OF ANIMALS AND ABLE TO SEE A 233 00:09:29,800 --> 00:09:30,800 NICE DOSE-RESPONSE, TIME 234 00:09:30,800 --> 00:09:32,760 COURSES, IN ANOTHER SPECIES, 235 00:09:32,760 --> 00:09:34,040 DIFFERENT TISSUES RESPOND AT 236 00:09:34,040 --> 00:09:36,120 DIFFERENT RATES BASED ON CELL 237 00:09:36,120 --> 00:09:36,880 POSITION RATE. 238 00:09:36,880 --> 00:09:39,280 DIRECT SEQUENCE WITH DNA ALLOWS 239 00:09:39,280 --> 00:09:41,960 US TO LOOK AT THE SPECTRUM, 240 00:09:41,960 --> 00:09:43,960 EXACT TYPE OF BASE CHANGES WITH 241 00:09:43,960 --> 00:09:45,840 MUTAGENS WHICH GIVES A SENSE OF 242 00:09:45,840 --> 00:09:46,200 MECHANISM. 243 00:09:46,200 --> 00:09:51,760 THIS IS AN EXAMPLE OF MOUSE 244 00:09:51,760 --> 00:09:55,280 TISSUE, MUTATIONAL PATTERN OF 245 00:09:55,280 --> 00:09:56,600 URETHANE IS DIFFERENT BETWEEN 246 00:09:56,600 --> 00:09:58,680 VEHICLE CONTROL ANIMAL ON THE 247 00:09:58,680 --> 00:10:01,640 OTHER SIDE. 248 00:10:01,640 --> 00:10:03,400 WE CAN ASSESS NUCLEOTIDE 249 00:10:03,400 --> 00:10:05,360 SIGNATURES, EVEN MORE NUANCED 250 00:10:05,360 --> 00:10:07,640 PATTERNS LOOKING AT PATTERNS OF 251 00:10:07,640 --> 00:10:09,720 BASE CHANGES AND CONSIDERING 252 00:10:09,720 --> 00:10:11,360 FLANKING ADJACENT BASES WHICH 253 00:10:11,360 --> 00:10:12,360 MODULATE SENSITIVITY TO CERTAIN 254 00:10:12,360 --> 00:10:14,680 MUTAGENS, AND THIS TYPE OF STUDY 255 00:10:14,680 --> 00:10:16,720 HAS BEEN USED TO SEQUENCE TUMORS 256 00:10:16,720 --> 00:10:18,120 IN HUMANS AND INFER MUTATIONAL 257 00:10:18,120 --> 00:10:20,680 PROCESS THAT LED TO TUMORS BUT 258 00:10:20,680 --> 00:10:23,840 NOW WE'RE ABLE TO AFTER A FEW 259 00:10:23,840 --> 00:10:25,920 DAYS OF EXPOSURE IDENTIFY THESE 260 00:10:25,920 --> 00:10:29,160 PATTERNS IN THE NORMAL TISSUES 261 00:10:29,160 --> 00:10:31,480 OF HEALTHY HUMANS OR CELLS IN 262 00:10:31,480 --> 00:10:33,400 CULTURE, ANIMALS, AND CAN YOU 263 00:10:33,400 --> 00:10:35,320 SEE DISTINCT PATTERNS THAT 264 00:10:35,320 --> 00:10:36,760 PROVIDE PRE-CLINICAL BRIDGING TO 265 00:10:36,760 --> 00:10:38,440 WHAT'S KNOWN IN CLINICAL 266 00:10:38,440 --> 00:10:39,720 MEDICINE NOW. 267 00:10:39,720 --> 00:10:44,000 THIS CAN BE APPLIED IN CELL 268 00:10:44,000 --> 00:10:45,920 CULTURE, APPLIED IN 269 00:10:45,920 --> 00:10:46,480 RECONSTRUCTIVE 3D TISSUE 270 00:10:46,480 --> 00:10:51,000 SYSTEMS, OR GAN ON A CHIP, MOVIG 271 00:10:51,000 --> 00:10:54,040 AWAY FROM AND REDUCING AMOUNT OF 272 00:10:54,040 --> 00:10:55,320 ANIMAL TESTING NEEDED, BEING 273 00:10:55,320 --> 00:10:56,800 ABLE TO USE THESE STIMULUS 274 00:10:56,800 --> 00:10:58,560 BECAUSE WE DON'T NEED 275 00:10:58,560 --> 00:11:00,720 GENETICALLY MODIFIED SYSTEM. 276 00:11:00,720 --> 00:11:02,400 ANY SOURCE OF DNA FROM ANY 277 00:11:02,400 --> 00:11:05,440 ORGANISM WILL WORK FOR THIS 278 00:11:05,440 --> 00:11:06,000 TECHNOLOGY. 279 00:11:06,000 --> 00:11:08,000 IT COMPANY APPLIED IN HUMANS 280 00:11:08,000 --> 00:11:08,240 DIRECTLY. 281 00:11:08,240 --> 00:11:10,480 THIS IS EXAMPLE OF BLOOD AND 282 00:11:10,480 --> 00:11:13,240 URINE FROM INDIVIDUALS WHO HAVE 283 00:11:13,240 --> 00:11:15,640 KNOWN EXPOSURE TO A CHEMICAL 284 00:11:15,640 --> 00:11:18,920 WHICH IS A KNOWN MUTAGENIC 285 00:11:18,920 --> 00:11:22,320 CHEMICAL, CAN BE -- IT'S 286 00:11:22,320 --> 00:11:26,360 ASSOCIATED WITH KIDNEY AND LIVER 287 00:11:26,360 --> 00:11:30,120 CANCER, AND NON-INVASIVE 288 00:11:30,120 --> 00:11:32,080 SAMPLING FROM HUMANS CAN SEE 289 00:11:32,080 --> 00:11:32,920 PATTERNS OF MUTATIONS, THIS 290 00:11:32,920 --> 00:11:34,920 OPENS THE OPPORTUNITY FOR OTHER 291 00:11:34,920 --> 00:11:37,560 STUDIES WE HAVE ONGOING WITH 292 00:11:37,560 --> 00:11:39,960 COLLABORATORS LOOKING IN OTHER 293 00:11:39,960 --> 00:11:41,280 INDIVIDUALS WITH OCCUPATIONAL 294 00:11:41,280 --> 00:11:43,160 EXPOSURES LIKE FIREFIGHTERS OR 295 00:11:43,160 --> 00:11:46,200 ASTRONAUTS OR MILITARY BURN PIT, 296 00:11:46,200 --> 00:11:48,480 SOMETHING WE HAVEN'T DONE, WE'RE 297 00:11:48,480 --> 00:11:51,280 INTERESTED IN BEING ABLE TO 298 00:11:51,280 --> 00:11:53,240 OBJECTIVELY MEASURE EXPOSURES IN 299 00:11:53,240 --> 00:11:56,920 A QUANTITATIVE WAY, EVEN IN 300 00:11:56,920 --> 00:11:58,800 NON-INVASIVE SAMPLING IN HUMANS. 301 00:11:58,800 --> 00:12:01,000 OUR ASK WE WANT TO BRING THIS 302 00:12:01,000 --> 00:12:04,280 TECHNOLOGY TO YOUR ATTENTION AND 303 00:12:04,280 --> 00:12:10,080 HELP RAISE AWARENESS, WE HAVE A 304 00:12:10,080 --> 00:12:11,960 LOT OF PUBLICATIONS YOU CAN LOOK 305 00:12:11,960 --> 00:12:12,280 AT. 306 00:12:12,280 --> 00:12:14,000 WE'RE INTERESTED IN YOUR HELP, 307 00:12:14,000 --> 00:12:17,080 GIVING GUIDANCE TO WHAT A 308 00:12:17,080 --> 00:12:17,840 REALISTIC REGULATORY PATHWAY 309 00:12:17,840 --> 00:12:20,920 MIGHT BE, THIS IS A CHALLENGING 310 00:12:20,920 --> 00:12:23,080 TECHNOLOGY INSOFAR AS IT HAS A 311 00:12:23,080 --> 00:12:25,760 LOT OF BROAD APPLICATIONS, CAN 312 00:12:25,760 --> 00:12:28,120 BE APPLIED IN VITRO, IN VIVO, TO 313 00:12:28,120 --> 00:12:29,680 ORGAN ON A CHIP, TO HUMANS, HOW 314 00:12:29,680 --> 00:12:33,320 DOES ONE THINK ABOUT A 315 00:12:33,320 --> 00:12:34,920 REGULATORY PATHWAY NOT SO 316 00:12:34,920 --> 00:12:36,920 PRESCRIPTIVE THAT IT REQUIRES 317 00:12:36,920 --> 00:12:39,560 ONE STRAIN OF ANIMALS OR CELL IN 318 00:12:39,560 --> 00:12:42,160 CULTURE BUT BROADLY CONSIDERED. 319 00:12:42,160 --> 00:12:48,960 HOW CAN IT BE USED AS ENDPOINT 320 00:12:48,960 --> 00:12:52,040 IN REGULATORY ASSAYS. 321 00:12:52,040 --> 00:12:55,840 WE'VE HEARD ABOUT DIFFERENT 322 00:12:55,840 --> 00:13:00,560 OPPORTUNITIES OF CASE STUDIES OR 323 00:13:00,560 --> 00:13:01,720 GUIDELINES, TEST GUIDELINES 324 00:13:01,720 --> 00:13:04,720 VERSUS CASE STUDIES VERSUS OTHER 325 00:13:04,720 --> 00:13:06,240 APPROACHES, AND INTERESTED WITH 326 00:13:06,240 --> 00:13:08,960 THIS, YOU KNOW, NEW SITUATION 327 00:13:08,960 --> 00:13:10,280 HOW ONE WOULD BEST GO ABOUT 328 00:13:10,280 --> 00:13:12,680 GETTING THIS OUT IN THE WORLD IN 329 00:13:12,680 --> 00:13:15,520 A WAY IT CAN BENEFIT THE 330 00:13:15,520 --> 00:13:15,800 COMMUNITY. 331 00:13:15,800 --> 00:13:17,200 WE'D LOVE YOUR IDEAS AND HOW 332 00:13:17,200 --> 00:13:19,160 THIS CAN BE APPLIED TO PROBLEMS 333 00:13:19,160 --> 00:13:21,600 RELEVANT TO YOU AND WE'D LOVE 334 00:13:21,600 --> 00:13:23,680 PARTNERSHIPS OF ANY AREAS YOU 335 00:13:23,680 --> 00:13:26,640 THINK WOULD BE RELEVANT. 336 00:13:26,640 --> 00:13:27,520 SO THANK YOU. 337 00:13:27,520 --> 00:13:28,160 >> GREAT. 338 00:13:28,160 --> 00:13:30,120 THANK YOU VERY MUCH, JESSE. 339 00:13:30,120 --> 00:13:35,040 [APPLAUSE] 340 00:13:35,040 --> 00:13:36,920 SO, MOVING TO PUBLIC 341 00:13:36,920 --> 00:13:39,320 COMMENTER -- I CAN PAUSE AND ASK 342 00:13:39,320 --> 00:13:41,840 IF THERE'S ANY CLARIFYING 343 00:13:41,840 --> 00:13:42,200 QUESTIONS. 344 00:13:42,200 --> 00:13:44,160 GO AHEAD, JOHN. 345 00:13:44,160 --> 00:13:46,400 ONE SECOND, WE'LL GET YOU THE 346 00:13:46,400 --> 00:13:49,480 MIC, JOHN. 347 00:13:49,480 --> 00:13:53,960 >> THANKS FOR THE TALK. 348 00:13:53,960 --> 00:13:54,880 INTERESTING. 349 00:13:54,880 --> 00:13:55,520 A LITTLE HEADS UP, WHATEVER 350 00:13:55,520 --> 00:13:56,840 DIRECTION YOU THINK YOU'RE 351 00:13:56,840 --> 00:13:58,920 HEADING WITH THIS, MOST 352 00:13:58,920 --> 00:14:01,440 REGULATORY AGENCIES HAVE 353 00:14:01,440 --> 00:14:03,080 GUIDANCE DOCUMENTS AVAILABLE. 354 00:14:03,080 --> 00:14:05,680 SO WHEN YOU'RE LOOKING FOR 355 00:14:05,680 --> 00:14:06,280 REGULATORY ACCEPTANCE, THINK 356 00:14:06,280 --> 00:14:07,560 ABOUT WHAT DIRECTION YOU'RE 357 00:14:07,560 --> 00:14:10,200 GOING WITH THIS, FIND THOSE 358 00:14:10,200 --> 00:14:12,640 GUIDANCES, AND CALL THOSE PEOPLE 359 00:14:12,640 --> 00:14:13,280 TOO. 360 00:14:13,280 --> 00:14:15,080 DON'T JUST READ THE DOCUMENT BUT 361 00:14:15,080 --> 00:14:16,280 CALL THOSE FOLKS, OR E-MAIL AND 362 00:14:16,280 --> 00:14:17,800 LET THEM KNOW YOU'RE DOING THIS 363 00:14:17,800 --> 00:14:19,640 SO THAT WHEN IT COMES TO THEIR 364 00:14:19,640 --> 00:14:21,520 DESK THEY WILL BE AWARE OF IT 365 00:14:21,520 --> 00:14:23,960 AND THEY WILL BE ABLE TO HELP 366 00:14:23,960 --> 00:14:24,600 AND GUIDE YOU. 367 00:14:24,600 --> 00:14:25,000 >> THANKS. 368 00:14:25,000 --> 00:14:27,000 YEAH, ONE OF THE CHALLENGES IS 369 00:14:27,000 --> 00:14:28,520 MANY OF THESE REGULATORY 370 00:14:28,520 --> 00:14:29,720 GUIDELINES HAVE BEEN -- THAT 371 00:14:29,720 --> 00:14:31,840 WE'VE SEEN HAVE BEEN REALLY 372 00:14:31,840 --> 00:14:33,880 FOCUSED ON A SPECIFIC IN VIVO 373 00:14:33,880 --> 00:14:38,080 ASSAY OR SPECIFIC IN VITRO 374 00:14:38,080 --> 00:14:38,360 ASSAY. 375 00:14:38,360 --> 00:14:40,360 AND THINKING ABOUT THIS, SORT OF 376 00:14:40,360 --> 00:14:42,000 A BROAD NEW APPROACH, HOW DOES 377 00:14:42,000 --> 00:14:47,720 ONE THINK ABOUT THAT IN THE 378 00:14:47,720 --> 00:14:50,200 CONTEXT OF PERHAPS EXACT TEST 379 00:14:50,200 --> 00:14:53,080 SYSTEM AGNOSTIC TOOL THAT CAN BE 380 00:14:53,080 --> 00:14:53,320 APPLIED. 381 00:14:53,320 --> 00:14:55,240 WE HAVEN'T SEEN A LOT OF 382 00:14:55,240 --> 00:14:57,880 GUIDANCE DOCUMENTS THAT TAKE 383 00:14:57,880 --> 00:14:58,840 THAT BROADER APPROACH, AND 384 00:14:58,840 --> 00:15:01,480 WONDERED WHAT YOUR THOUGHTS WERE 385 00:15:01,480 --> 00:15:01,720 ON THAT. 386 00:15:01,720 --> 00:15:05,520 >> SOME OF THEM ARE FAIRLY 387 00:15:05,520 --> 00:15:06,080 BROAD. 388 00:15:06,080 --> 00:15:08,360 FDA, EPA, DoD, CPSC ALL HAVE 389 00:15:08,360 --> 00:15:12,880 GUIDANCE OUT THERE FAIRLY BROAD 390 00:15:12,880 --> 00:15:13,840 IN THEIR APPROACH, BUT ALSO 391 00:15:13,840 --> 00:15:16,320 THINK ABOUT WHERE YOU'RE TAKING 392 00:15:16,320 --> 00:15:19,000 THIS AND CONTACT THE -- MAYBE 393 00:15:19,000 --> 00:15:20,000 THE ICCVAM REPRESENTATIVE OR 394 00:15:20,000 --> 00:15:24,240 WHOEVER YOU'RE TAKING THIS TO, 395 00:15:24,240 --> 00:15:29,240 LIKE CPSC GET HOLD OF ME, FOR 396 00:15:29,240 --> 00:15:30,040 FDA SUZIE FITZPATRICK, WE'RE ALL 397 00:15:30,040 --> 00:15:32,200 HAPPY TO DISCUSS WHAT YOU NEED 398 00:15:32,200 --> 00:15:32,600 TO DO. 399 00:15:32,600 --> 00:15:33,400 >>AWESOME. 400 00:15:33,400 --> 00:15:34,960 WE'LL REACH OUT. 401 00:15:34,960 --> 00:15:35,200 THANK YOU. 402 00:15:35,200 --> 00:15:36,360 >> THANKS, JOHN. 403 00:15:36,360 --> 00:15:37,560 I WILL ADD THAT THAT IS 404 00:15:37,560 --> 00:15:40,960 ABSOLUTELY ONE OF THE OBJECTIVES 405 00:15:40,960 --> 00:15:43,160 OF HAVING PUBLIC COMMENTERS JOIN 406 00:15:43,160 --> 00:15:45,560 THE ICCVAM PUBLIC FORUM TO RAISE 407 00:15:45,560 --> 00:15:48,520 AWARENESS OF THESE TECHNOLOGIES 408 00:15:48,520 --> 00:15:50,840 FOR POTENTIAL AGENCY USE AND 409 00:15:50,840 --> 00:15:53,480 I'LL ADD THE NIEHS DIVISION OF 410 00:15:53,480 --> 00:15:57,160 TRANSLATIONAL TOXICOLOGY WORKED 411 00:15:57,160 --> 00:15:58,160 EXTENSIVELY WITH TWINSTRAND 412 00:15:58,160 --> 00:15:59,160 BIOSCIENCE AND HEALTH CANADA, 413 00:15:59,160 --> 00:16:01,440 THERE'S BEEN QUITE A BIT OF 414 00:16:01,440 --> 00:16:04,600 INITIAL WORK DONE IN LOOKING AT 415 00:16:04,600 --> 00:16:05,480 THE UTILITY. 416 00:16:05,480 --> 00:16:07,240 IN THE INTEREST OF TIME I'M 417 00:16:07,240 --> 00:16:12,640 GOING TO MOVE TO OUR NEXT PUBLIC 418 00:16:12,640 --> 00:16:14,280 COMMENTER, AMY KYLE FROM -- 419 00:16:14,280 --> 00:16:15,800 RETIRED FROM UC-BERKELEY. 420 00:16:15,800 --> 00:16:20,200 ARE YOU ONLINE? 421 00:16:20,200 --> 00:16:20,720 >> I AM. 422 00:16:20,720 --> 00:16:21,040 >> GREAT. 423 00:16:21,040 --> 00:16:22,360 DO YOU HAVE SLIDES YOU WOULD 424 00:16:22,360 --> 00:16:25,560 LIKE TO SHARE OR WILL YOU JUST 425 00:16:25,560 --> 00:16:26,680 BE PROVIDING ORAL COMMENT? 426 00:16:26,680 --> 00:16:29,280 >> I DO HAVE A FEW SLIDES. 427 00:16:29,280 --> 00:16:32,120 SO CAN I SHARE MY SCREEN? 428 00:16:32,120 --> 00:16:32,440 >>ABSOLUTELY. 429 00:16:32,440 --> 00:16:34,400 YOU SHOULD BE ABLE TO HIT THE 430 00:16:34,400 --> 00:16:37,400 GREEN BUTTON AND HOPEFULLY IT 431 00:16:37,400 --> 00:16:38,320 WILL WORK SEAMLESSLY. 432 00:16:38,320 --> 00:16:39,560 >>OKAY. 433 00:16:39,560 --> 00:16:42,280 HELLO FIRST. 434 00:16:42,280 --> 00:16:42,600 LET'S SEE. 435 00:16:42,600 --> 00:16:45,120 >>WE'RE SEEING SOME KIND OF 436 00:16:45,120 --> 00:16:47,240 VIDEO FEED BUT IT'S NOT SLIDES. 437 00:16:47,240 --> 00:16:50,160 NOW WE SEE YOU. 438 00:16:50,160 --> 00:16:50,440 WONDERFUL. 439 00:16:50,440 --> 00:16:50,680 >> OKAY. 440 00:16:50,680 --> 00:16:52,680 I WANT TO SAY HELLO. 441 00:16:52,680 --> 00:16:53,680 >> GREAT. 442 00:16:53,680 --> 00:16:57,840 >> I'M NOT A ROBOT. 443 00:16:57,840 --> 00:17:03,000 LET'S SEE IF I CAN GET THIS UP 444 00:17:03,000 --> 00:17:05,720 HERE. 445 00:17:05,720 --> 00:17:07,120 THE LITTLE THINGS COVER UP THE 446 00:17:07,120 --> 00:17:16,120 THING YOU NEED TO CLICK HERE. 447 00:17:16,120 --> 00:17:18,520 >> CLICK ON SLIDE SHOW UP 448 00:17:18,520 --> 00:17:21,680 ABOVE, THREE OVER FROM VIEW. 449 00:17:21,680 --> 00:17:27,480 >> OKAY I ALWAYS CLICK ON THE 450 00:17:27,480 --> 00:17:27,720 BOTTOM. 451 00:17:27,720 --> 00:17:28,800 >> ALMOST. 452 00:17:28,800 --> 00:17:32,000 KEEP GOING TO THE LEFT. 453 00:17:32,000 --> 00:17:36,120 >> THANK YOU SO MUCH. 454 00:17:36,120 --> 00:17:36,760 >> NO WORRIES. 455 00:17:36,760 --> 00:17:39,440 >> THAT DOESN'T SEEM TO BE 456 00:17:39,440 --> 00:17:39,800 WORKING. 457 00:17:39,800 --> 00:17:41,280 >> CLICK FROM BEGINNING, TOP 458 00:17:41,280 --> 00:17:45,440 LEFT BUTTON UNDER THAT MENU. 459 00:17:45,440 --> 00:17:48,960 >> I USUALLY USE LOWER BUTTONS, 460 00:17:48,960 --> 00:17:50,600 I'M NOT AS ADAPTABLE AS I SHOULD 461 00:17:50,600 --> 00:17:50,800 BE. 462 00:17:50,800 --> 00:17:52,640 THANK YOU FOR HAVING ME. 463 00:17:52,640 --> 00:17:54,320 I APPRECIATE THE PUBLIC COMMENT. 464 00:17:54,320 --> 00:17:55,520 I'VE GOTTEN A LOT OUT OF THE 465 00:17:55,520 --> 00:17:56,400 FORUM TOO. 466 00:17:56,400 --> 00:18:01,440 I APPRECIATE ALL OF THE 467 00:18:01,440 --> 00:18:02,200 PRESENTATIONS AND SPEAKERS. 468 00:18:02,200 --> 00:18:03,520 WHY AM I HERE? 469 00:18:03,520 --> 00:18:07,360 I'M RETIRED NOW BUT MY WORK IS 470 00:18:07,360 --> 00:18:10,640 AND HAS BEEN ABOUT HOW WE USE 471 00:18:10,640 --> 00:18:12,600 INFORMATION IN PUBLIC POLICY. 472 00:18:12,600 --> 00:18:14,920 I STARTED MY CAREER IN PUBLIC 473 00:18:14,920 --> 00:18:17,320 SERVICE, I WAS A REGULATOR FOR A 474 00:18:17,320 --> 00:18:20,040 NUMBER OF YEARS AND MY SECOND 475 00:18:20,040 --> 00:18:22,120 CAREER WAS IN ACADEMIA AT 476 00:18:22,120 --> 00:18:24,080 UC-BERKELEY WHERE I WORKED ON A 477 00:18:24,080 --> 00:18:27,680 LOT OF RESEARCH TRANSLATION AND 478 00:18:27,680 --> 00:18:29,800 ENGAGEMENT ISSUES FROM THE 479 00:18:29,800 --> 00:18:31,680 PERSPECTIVE OF PROGRAM DEVOTED 480 00:18:31,680 --> 00:18:35,480 TO ENVIRONMENTAL HEALTH 481 00:18:35,480 --> 00:18:35,760 SCIENCES. 482 00:18:35,760 --> 00:18:37,560 AND I AM VERY INTERESTED IN ALL 483 00:18:37,560 --> 00:18:41,080 THIS WORK AND WHAT IT CAN DO, 484 00:18:41,080 --> 00:18:43,600 HOW WE CAN BRING IT FORWARD IN A 485 00:18:43,600 --> 00:18:46,200 WAY THAT HELPS US THE MOST WITH 486 00:18:46,200 --> 00:18:47,200 ADDRESSING THE ENVIRONMENTAL 487 00:18:47,200 --> 00:18:50,040 HEALTH ISSUES THAT WE HAVE. 488 00:18:50,040 --> 00:18:52,800 I WORK A LOT WITH PEOPLE WHO 489 00:18:52,800 --> 00:18:55,360 ARE -- HAVE MORE OF A LAY 490 00:18:55,360 --> 00:18:56,200 BACKGROUND. 491 00:18:56,200 --> 00:18:58,360 WE CALL THEM ENGAGED LAY 492 00:18:58,360 --> 00:19:00,120 AUDIENCE, PEOPLE INTERESTED AND 493 00:19:00,120 --> 00:19:01,720 DEVOTED TO THESE ISSUES BUT 494 00:19:01,720 --> 00:19:03,720 DON'T A LOT OR MAYBE ANY 495 00:19:03,720 --> 00:19:04,960 SCIENTIFIC TRAINING. 496 00:19:04,960 --> 00:19:07,080 I WRITE A LOT OF THINGS THAT 497 00:19:07,080 --> 00:19:09,320 START WITH QUESTIONS LIKE, WHAT 498 00:19:09,320 --> 00:19:10,200 IS NAMs? 499 00:19:10,200 --> 00:19:14,520 OR WHAT ARE AIR TOX, THINGS LIKE 500 00:19:14,520 --> 00:19:18,160 THAT, TO TRY TO HELP ALLOW FOR 501 00:19:18,160 --> 00:19:19,160 DIALOGUE AND DISCUSSION AND 502 00:19:19,160 --> 00:19:20,000 CONSULTATION, PEOPLE WHO DON'T 503 00:19:20,000 --> 00:19:21,640 SPEAK THIS LANGUAGE AT ALL AND 504 00:19:21,640 --> 00:19:22,400 NEVER WILL. 505 00:19:22,400 --> 00:19:25,960 IT'S NOT A QUESTION OF SCIENCE 506 00:19:25,960 --> 00:19:26,600 EDUCATION PARTICULARLY BECAUSE 507 00:19:26,600 --> 00:19:29,840 PEOPLE DON'T HAVE TIME TO LEARN 508 00:19:29,840 --> 00:19:30,720 ALL THIS. 509 00:19:30,720 --> 00:19:33,160 BUT STILL THERE'S A NEED FOR THE 510 00:19:33,160 --> 00:19:37,000 PEOPLE WHO ARE BEING SPOKEN FOR 511 00:19:37,000 --> 00:19:38,840 IN SOME WAY OR REPRESENTED WHOSE 512 00:19:38,840 --> 00:19:40,360 NEEDS NEED TO BE MET HERE TO 513 00:19:40,360 --> 00:19:43,440 HAVE A WAY OF ENGAGING AND 514 00:19:43,440 --> 00:19:44,520 UNDERSTANDING. 515 00:19:44,520 --> 00:19:45,640 AND BRINGING THEIR PERSPECTIVE 516 00:19:45,640 --> 00:19:47,040 AND INPUT HERE. 517 00:19:47,040 --> 00:19:49,640 AND I THINK THAT'S IN THE 518 00:19:49,640 --> 00:19:51,080 FUTURE, BUT WHAT I'M LOOKING 519 00:19:51,080 --> 00:19:53,800 TOWARD AND THAT'S WHY I'M HERE. 520 00:19:53,800 --> 00:19:55,680 IT SEEMS RANDOM, WHAT ARE YOU 521 00:19:55,680 --> 00:19:56,880 DOING HERE, AMY? 522 00:19:56,880 --> 00:20:00,600 YOU'RE NOT DROPPING ANY OF THESE 523 00:20:00,600 --> 00:20:01,040 METHODS. 524 00:20:01,040 --> 00:20:02,600 BETTER METHODS ARE CRUCIAL 525 00:20:02,600 --> 00:20:02,920 THOUGH. 526 00:20:02,920 --> 00:20:05,520 I ALSO WANT TO SAY I REALLY 527 00:20:05,520 --> 00:20:07,040 APPRECIATE THE QUALITY OF WORK, 528 00:20:07,040 --> 00:20:10,560 BRILLIANCE OF SOME OF THIS WORK 529 00:20:10,560 --> 00:20:12,200 THAT IT'S STUNNING. 530 00:20:12,200 --> 00:20:12,880 IT'S INSPIRING. 531 00:20:12,880 --> 00:20:15,720 ACTUALLY I THINK I HAVE THIS ON 532 00:20:15,720 --> 00:20:16,800 MY SLIDE. 533 00:20:16,800 --> 00:20:18,320 IT'S IMPRESSIVE, IMPORTANT, 534 00:20:18,320 --> 00:20:19,200 INSPIRING, THREE Is. 535 00:20:19,200 --> 00:20:21,160 I WANT TO ACKNOWLEDGE THAT. 536 00:20:21,160 --> 00:20:26,200 THAT THERE'S A HUGE AMOUNT OF 537 00:20:26,200 --> 00:20:27,080 INSIGHT AND KNOWLEDGE THAT'S 538 00:20:27,080 --> 00:20:28,840 GONE INTO ALL OF THIS. 539 00:20:28,840 --> 00:20:30,800 I HONOR THAT EVEN AS I'M GOING 540 00:20:30,800 --> 00:20:33,200 TO SAY SOME THINGS THAT I THINK 541 00:20:33,200 --> 00:20:34,960 NEED MORE ATTENTION. 542 00:20:34,960 --> 00:20:36,840 BUT IT'S THIS SPIRIT OF MAKING 543 00:20:36,840 --> 00:20:39,440 THE HIGHEST AND BEST USE OUT OF 544 00:20:39,440 --> 00:20:42,080 THIS, THESE INVESTMENTS AND THIS 545 00:20:42,080 --> 00:20:42,280 TIME. 546 00:20:42,280 --> 00:20:44,480 I HAVE THREE MAIN POINTS. 547 00:20:44,480 --> 00:20:48,520 CONFIDENCE, SHOWING UP IN YOUR 548 00:20:48,520 --> 00:20:51,400 TALK, THE THREE Cs AND I'M NOT 549 00:20:51,400 --> 00:20:53,920 SURE IF THAT'S ONE OF THE THREE 550 00:20:53,920 --> 00:20:55,680 Cs BUT DISCUSSIONS OF 551 00:20:55,680 --> 00:20:56,160 FRAMEWORKS, ISSUES OF 552 00:20:56,160 --> 00:20:57,320 COMMUNICATION ARE SO KEY TO 553 00:20:57,320 --> 00:20:57,520 THAT. 554 00:20:57,520 --> 00:20:59,040 I'VE BEEN HERE BEFORE TO TALK 555 00:20:59,040 --> 00:21:00,480 ABOUT THAT. 556 00:21:00,480 --> 00:21:02,000 I SEE PROGRESS SO I HAVE A FEW 557 00:21:02,000 --> 00:21:04,200 THINGS TO SAY ABOUT THAT. 558 00:21:04,200 --> 00:21:06,320 SECOND MOST IMPORTANT THING IS 559 00:21:06,320 --> 00:21:09,840 HOW TO ENVISION WHO ARE THE FULL 560 00:21:09,840 --> 00:21:13,080 RANGE OF STAKEHOLDERS HERE. 561 00:21:13,080 --> 00:21:15,200 BECAUSE THIS WORK IS ENGAGING 562 00:21:15,200 --> 00:21:17,440 PEOPLE FROM A CERTAIN PART OF 563 00:21:17,440 --> 00:21:19,080 THE COMMUNITY BUT I THINK IT 564 00:21:19,080 --> 00:21:21,080 NEEDS TO ALSO FIGURE OUT HOW TO 565 00:21:21,080 --> 00:21:22,360 BRING IN THE FULL COMMUNITY. 566 00:21:22,360 --> 00:21:26,720 AND THEN MY LAST POINT IS ABOUT 567 00:21:26,720 --> 00:21:30,920 HOW CAN THIS BE APPLIED TO MORE 568 00:21:30,920 --> 00:21:31,560 FUTURE-LOOKING UNDERSTANDING OF 569 00:21:31,560 --> 00:21:35,160 WHAT WE NEED TO KNOW AND ACT ON. 570 00:21:35,160 --> 00:21:39,560 AND OF COURSE IT STARTED OUT -- 571 00:21:39,560 --> 00:21:42,520 STARTS OUT AS REPLACING EXISTING 572 00:21:42,520 --> 00:21:43,280 METHODS WITHOUT USING ANIMALS 573 00:21:43,280 --> 00:21:44,320 WHICH I THINK EVERYONE SUPPORTS 574 00:21:44,320 --> 00:21:46,240 THAT, AS LONG AS THE NEW METHODS 575 00:21:46,240 --> 00:21:47,440 WORK. 576 00:21:47,440 --> 00:21:49,520 I'M NOT SURE ANYONE'S IN FAVOR 577 00:21:49,520 --> 00:21:52,120 OF MORE UNNECESSARY USE OF 578 00:21:52,120 --> 00:21:52,600 ANIMALS. 579 00:21:52,600 --> 00:21:54,200 BUT ALSO THERE ARE OTHER 580 00:21:54,200 --> 00:21:56,320 QUESTIONS OUT THERE BEYOND THAT. 581 00:21:56,320 --> 00:21:58,120 SO DO WE HAVE TO ONLY REPLACE 582 00:21:58,120 --> 00:22:01,640 THE METHODS THAT WE HAVE OR CAN 583 00:22:01,640 --> 00:22:05,280 WE TAKE ON NEW BIGGER ISSUES 584 00:22:05,280 --> 00:22:08,240 THAT MAYBE MAKE IT BETTER, NOT 585 00:22:08,240 --> 00:22:09,200 JUST LESS ANIMALS. 586 00:22:09,200 --> 00:22:11,120 SO THOSE ARE MY MAIN POINTS. 587 00:22:11,120 --> 00:22:14,800 AND I'M GOING TO TRY TO MOVE 588 00:22:14,800 --> 00:22:16,040 QUICKLY, YOU HAVE A LOT OF 589 00:22:16,040 --> 00:22:18,240 PEOPLE TO HEAR FROM. 590 00:22:18,240 --> 00:22:19,760 CONFIDENCE, GO BACK TO 591 00:22:19,760 --> 00:22:20,200 CONFIDENCE. 592 00:22:20,200 --> 00:22:23,480 IN METHODS FOR REGULATION FOR 593 00:22:23,480 --> 00:22:25,880 PUBLIC HEALTH IT NEEDS TO EXTEND 594 00:22:25,880 --> 00:22:26,880 BEYOND THIS AUDIENCE TO PEOPLE 595 00:22:26,880 --> 00:22:28,480 INVOLVED ONCE YOU GET TO THE 596 00:22:28,480 --> 00:22:29,520 REGULATORY SIDE. 597 00:22:29,520 --> 00:22:30,280 THIS INCLUDES WORKERS, PEOPLE 598 00:22:30,280 --> 00:22:33,960 WHO LIVE OR WORK IN HIGHLY 599 00:22:33,960 --> 00:22:37,160 IMPACTED COMMUNITIES, YOU KNOW, 600 00:22:37,160 --> 00:22:42,080 OTHER KINDS AS WELL BECAUSE 601 00:22:42,080 --> 00:22:43,600 REGULATORY ACTIONS OCCUR OUTSIDE 602 00:22:43,600 --> 00:22:45,360 CONFINES OF THE SCIENTIFIC 603 00:22:45,360 --> 00:22:48,200 COMMUNITY AND RESPOND TO OTHER 604 00:22:48,200 --> 00:22:49,280 IMPERATIVES AND INPUTS, ET 605 00:22:49,280 --> 00:22:49,880 CETERA. 606 00:22:49,880 --> 00:22:50,800 PEOPLE ARE PARTICIPATING IN 607 00:22:50,800 --> 00:22:53,440 THAT, NEED TO BE ABLE TO AT 608 00:22:53,440 --> 00:22:56,640 LEAST HAVE A FUNCTIONAL 609 00:22:56,640 --> 00:22:59,360 UNDERSTANDING OF WHAT IT'S BASED 610 00:22:59,360 --> 00:22:59,680 ON. 611 00:22:59,680 --> 00:23:01,880 SO SOMEHOW THAT NEEDS TO EXTEND 612 00:23:01,880 --> 00:23:02,120 OUT. 613 00:23:02,120 --> 00:23:04,080 AND THERE'S LOTS OF THINGS ABOUT 614 00:23:04,080 --> 00:23:06,360 HOW THAT CAN BE DONE AND IT 615 00:23:06,360 --> 00:23:07,560 CAN'T BE DONE BY TEACHING 616 00:23:07,560 --> 00:23:09,440 EVERYONE ALL OF WHAT YOU KNOW, I 617 00:23:09,440 --> 00:23:12,160 KNOW THAT, BUT THERE ARE WAYS TO 618 00:23:12,160 --> 00:23:14,560 CONNECT KEY HAND-HOLDS AND SET 619 00:23:14,560 --> 00:23:16,120 UP MAYBE WHAT SOME PEOPLE CALL 620 00:23:16,120 --> 00:23:18,000 CIRCLES OF TRUST OR ENGAGEMENT 621 00:23:18,000 --> 00:23:19,160 THAT CAN REACH OUT BEYOND WHERE 622 00:23:19,160 --> 00:23:21,120 YOU ARE NOW. 623 00:23:21,120 --> 00:23:22,360 I THINK THAT'S AN IMPORTANT 624 00:23:22,360 --> 00:23:24,640 THING TO DO. 625 00:23:24,640 --> 00:23:27,280 THE QUESTION OF COMMUNICATION 626 00:23:27,280 --> 00:23:33,520 ALSO IS VERY KEY, HOW TO DEVELOP 627 00:23:33,520 --> 00:23:35,680 BOTH VOCABULARY IS IMPORTANT. 628 00:23:35,680 --> 00:23:37,760 I'VE NOTICED THIS TIME THERE'S 629 00:23:37,760 --> 00:23:40,840 LESS ACRONYMS AND MORE OF THE 630 00:23:40,840 --> 00:23:41,720 PRESENTATIONS ARE 631 00:23:41,720 --> 00:23:43,560 UNDERSTANDABLE, EVEN TO ME. 632 00:23:43,560 --> 00:23:45,880 I CAN FEEL LIKE THERE'S BEEN 633 00:23:45,880 --> 00:23:49,520 SOME EMPHASIS ON SPEAKING ACROSS 634 00:23:49,520 --> 00:23:51,000 DISCIPLINES AND OUT MAYBE BEYOND 635 00:23:51,000 --> 00:23:52,360 A LAB CONTEXT. 636 00:23:52,360 --> 00:23:53,000 I APPRECIATE THAT. 637 00:23:53,000 --> 00:23:54,440 I THINK THERE'S MORE THAT NEEDS 638 00:23:54,440 --> 00:23:57,040 TO BE DONE IN THAT SPECIFIC 639 00:23:57,040 --> 00:24:01,080 FOCUSED WAY TO BUILD SOME 640 00:24:01,080 --> 00:24:02,640 VOCABULARY THAT CAN LINK WORK 641 00:24:02,640 --> 00:24:05,560 AND IDEAS THAT HAVE NO 642 00:24:05,560 --> 00:24:07,560 TRANSLATION RIGHT NOW INTO A 643 00:24:07,560 --> 00:24:08,680 PUBLIC DISCOURSE. 644 00:24:08,680 --> 00:24:10,840 AND THEN ALSO THE OTHER THING 645 00:24:10,840 --> 00:24:12,800 THAT'S REALLY IMPORTANT ARE SOME 646 00:24:12,800 --> 00:24:16,960 OF THE METRICS USED TO DESCRIBE 647 00:24:16,960 --> 00:24:20,800 THESE -- THE IMPACT OR IMPORT OF 648 00:24:20,800 --> 00:24:22,120 VARIOUS METHODS, THE 649 00:24:22,120 --> 00:24:24,080 REPRESENTATIVE FROM NIST 650 00:24:24,080 --> 00:24:27,480 YESTERDAY WAS TALKING ABOUT HOW 651 00:24:27,480 --> 00:24:30,880 TO FRAME THINGS AS RATES OF 652 00:24:30,880 --> 00:24:31,360 FALSE NEGATIVES, FALSE 653 00:24:31,360 --> 00:24:33,480 POSITIVES, FOR EXAMPLE. 654 00:24:33,480 --> 00:24:37,240 A CONCEPT LIKE THAT IS VERY 655 00:24:37,240 --> 00:24:38,520 IMPORTANT, IT MATTERS TO RULE 656 00:24:38,520 --> 00:24:40,840 THINGS IN, RULE THINGS OUT, HOW 657 00:24:40,840 --> 00:24:45,320 WELL YOUR TESTS CAN DO THAT IS 658 00:24:45,320 --> 00:24:46,520 FUNDAMENTALLY ESSENTIAL QUESTION 659 00:24:46,520 --> 00:24:48,040 TO TIERED FRAMEWORKS, ALSO TO 660 00:24:48,040 --> 00:24:49,960 HOW THOSE ARE INTERPRETED IN A 661 00:24:49,960 --> 00:24:50,720 POLICY CONTEXT. 662 00:24:50,720 --> 00:24:53,120 I THINK THAT MIGHT NOT BE THE 663 00:24:53,120 --> 00:24:54,320 RIGHT METAPHOR BUT THAT'S 664 00:24:54,320 --> 00:24:57,600 SOMETHING THAT PEOPLE CAN 665 00:24:57,600 --> 00:25:00,680 UNDERSTAND AND EXIST OUTSIDE THE 666 00:25:00,680 --> 00:25:01,920 NAMs BUBBLE. 667 00:25:01,920 --> 00:25:03,960 I DON'T MEAN ANY DISRESPECT BY 668 00:25:03,960 --> 00:25:06,600 THAT BUT IT IS A WORLD THAT HAS 669 00:25:06,600 --> 00:25:09,280 ITS OWN -- IT CAN BE DEFINED AND 670 00:25:09,280 --> 00:25:14,760 HAS ITS OWN VOCABULARY. 671 00:25:14,760 --> 00:25:16,880 I WOULD RECOMMEND FOCUSED 672 00:25:16,880 --> 00:25:19,720 ATTENTION. 673 00:25:19,720 --> 00:25:21,440 HE MENTIONED CONFIDENCE 674 00:25:21,440 --> 00:25:23,080 INTERVALS, STATISTICAL METRICS 675 00:25:23,080 --> 00:25:25,080 ARE MORE COMPLICATED BUT THINGS 676 00:25:25,080 --> 00:25:27,160 THAT CAN BE USED CONSISTENTLY 677 00:25:27,160 --> 00:25:29,640 ACROSS TESTS OR ACROSS 678 00:25:29,640 --> 00:25:30,840 APPROACHES, AND THEN PEOPLE CAN 679 00:25:30,840 --> 00:25:32,720 COME TO UNDERSTAND WHAT THEY 680 00:25:32,720 --> 00:25:33,600 MEAN. 681 00:25:33,600 --> 00:25:37,760 THEY ARE USE CONSISTENTLY, THEY 682 00:25:37,760 --> 00:25:41,680 CAN BE MORE COMPLICATED BUT 683 00:25:41,680 --> 00:25:42,040 STILL USEFUL. 684 00:25:42,040 --> 00:25:43,440 AGAIN, THERE'S A LOT OF PLAYERS. 685 00:25:43,440 --> 00:25:45,080 YOU CAN LOOK AT ANY DOCKET TO 686 00:25:45,080 --> 00:25:47,720 SEE THE RANGE OF PLAYERS THAT 687 00:25:47,720 --> 00:25:49,560 NEED TO HAVE SOME DEGREE OF 688 00:25:49,560 --> 00:25:51,560 CONTACT WITH THE SCIENTIFIC 689 00:25:51,560 --> 00:25:52,520 BASIS FOR REGULATIONS. 690 00:25:52,520 --> 00:25:55,600 AND I DON'T KNOW IF THIS IS 691 00:25:55,600 --> 00:25:56,960 POLITICALLY INCORRECT TO BRING 692 00:25:56,960 --> 00:26:01,320 UP, IT MIGHT BE, BUT THERE'S 693 00:26:01,320 --> 00:26:04,040 ALSO THE LITIGATION COMPONENT OF 694 00:26:04,040 --> 00:26:05,800 REGULATORY ACTIONS, IN THAT MOST 695 00:26:05,800 --> 00:26:07,800 OF THE IMPORTANT REGULATIONS ARE 696 00:26:07,800 --> 00:26:10,440 LITIGATED, AND CAN BE BY BOTH 697 00:26:10,440 --> 00:26:13,680 SIDES, OR FROM MULTIPLE 698 00:26:13,680 --> 00:26:14,040 PERSPECTIVES. 699 00:26:14,040 --> 00:26:15,120 BUT THAT BRINGS US TO THE 700 00:26:15,120 --> 00:26:20,920 QUESTION WHAT ABOUT THE 701 00:26:20,920 --> 00:26:21,880 JUDICIARY? 702 00:26:21,880 --> 00:26:23,520 WHAT CAN BE COMMUNICATED TO 703 00:26:23,520 --> 00:26:23,720 THEM? 704 00:26:23,720 --> 00:26:25,320 I'M JUST GOING TO SAY THIS OUT 705 00:26:25,320 --> 00:26:25,720 LOUD. 706 00:26:25,720 --> 00:26:27,800 I DON'T KNOW, MAYBE I SHOULDN'T, 707 00:26:27,800 --> 00:26:30,760 BUT THERE ARE ENTITIES YOU'RE 708 00:26:30,760 --> 00:26:33,280 USING 1980 STYLE RULES AND 709 00:26:33,280 --> 00:26:37,840 ASSAYS BECAUSE THOSE HAVE 710 00:26:37,840 --> 00:26:39,400 SURVIVED JUDICIAL REVIEW, NOT 711 00:26:39,400 --> 00:26:42,000 THE ONLY REASON, BUT NEW ISN'T 712 00:26:42,000 --> 00:26:44,760 GOOD IF NO JUDGE WILL TRUST IT, 713 00:26:44,760 --> 00:26:46,400 AND I THINK THE PROGRESS THAT 714 00:26:46,400 --> 00:26:49,040 COULD BE MADE TOWARDS SOME OF 715 00:26:49,040 --> 00:26:52,960 THESE METHODS IS GOING TO NEED 716 00:26:52,960 --> 00:26:55,040 EVOLUTION AND UNDERSTAND. 717 00:26:55,040 --> 00:26:59,200 THAT'S MY FIRST MAIN POINT. 718 00:26:59,200 --> 00:27:00,600 MY SECOND -- MY THIRD POINT ON 719 00:27:00,600 --> 00:27:02,320 THE SLIDE IN TERMS OF 720 00:27:02,320 --> 00:27:07,120 ENCOMPASSING THE NEEDS OF THE 721 00:27:07,120 --> 00:27:07,960 FUTURE LET'S NOT REMODELEL HOUSE 722 00:27:07,960 --> 00:27:09,720 WE HAVE. 723 00:27:09,720 --> 00:27:11,880 LET'S MAKE IT A BETTER ONE AND 724 00:27:11,880 --> 00:27:14,640 THINK ABOUT SOME OF THESE 725 00:27:14,640 --> 00:27:17,480 CRITICAL CHALLENGES AND I ASKED 726 00:27:17,480 --> 00:27:20,440 THE QUESTION YESTERDAY ABOUT IS 727 00:27:20,440 --> 00:27:22,240 ANYBODY CONSIDERING ANY ASPECTS 728 00:27:22,240 --> 00:27:25,160 OF WHAT WE CALL REALITY BASED 729 00:27:25,160 --> 00:27:26,600 METHODS, SORT OF THIS LINE FOR 730 00:27:26,600 --> 00:27:29,200 THAT, BUT METHODS THAT CAN LOOK 731 00:27:29,200 --> 00:27:31,400 AT THE ACTUAL COMBINATIONS OF 732 00:27:31,400 --> 00:27:40,400 CHEMICALS, PERHAPS IN THIS CASE, 733 00:27:40,400 --> 00:27:42,160 BUT ALSO PERHAPS SUSCEPTIBILITY 734 00:27:42,160 --> 00:27:43,160 METRICS AND ENVIRONMENTAL 735 00:27:43,160 --> 00:27:45,560 REALITIES PEOPLE ACTUALLY LIVE 736 00:27:45,560 --> 00:27:47,960 IN, CHEMICAL METHODS JUST DON'T 737 00:27:47,960 --> 00:27:49,280 DO THAT. 738 00:27:49,280 --> 00:27:55,760 THAT NEEDS TO BE DONE IN A WAY, 739 00:27:55,760 --> 00:27:58,160 INTERAGENCY, INTERMETRIC, 740 00:27:58,160 --> 00:28:06,600 INTERENVIRONMENT APPROACH LIKE 741 00:28:06,600 --> 00:28:08,880 YOU'VE ESTABLISHED AT ICCVAM. 742 00:28:08,880 --> 00:28:10,560 AT EPA DIFFERENT OFFERSES HAVE 743 00:28:10,560 --> 00:28:12,360 DIFFERENT PIECE, ACROSS THE 744 00:28:12,360 --> 00:28:12,960 FEDERAL SPECTRUM DIFFERENT 745 00:28:12,960 --> 00:28:14,000 AGENCIES HAVE DIFFERENT PIECES 746 00:28:14,000 --> 00:28:14,760 OF IT. 747 00:28:14,760 --> 00:28:17,840 AND SO THE MODEL OF THINKING 748 00:28:17,840 --> 00:28:20,680 TOGETHER AND PLANNING TOGETHER 749 00:28:20,680 --> 00:28:23,440 AND HARMONIZING IN WAYS THAT CAN 750 00:28:23,440 --> 00:28:25,720 ADVANCE THIS, I KNOW IT'S NOT 751 00:28:25,720 --> 00:28:27,760 EXACTLY THE LEGAL MANDATE OF 752 00:28:27,760 --> 00:28:30,320 ICCVAM BUT MAYBE IT IS IN SOME 753 00:28:30,320 --> 00:28:33,160 WAY IN THAT YOU'RE SUPPOSED TO 754 00:28:33,160 --> 00:28:35,600 BE ALSO PROVIDING EVIDENCE THAT 755 00:28:35,600 --> 00:28:38,000 CAN BE USED FOR ENVIRONMENTAL 756 00:28:38,000 --> 00:28:39,960 HEALTH AND ENVIRONMENTAL 757 00:28:39,960 --> 00:28:40,280 PROTECTION. 758 00:28:40,280 --> 00:28:41,600 AND SO MAYBE THERE'S SOME PART 759 00:28:41,600 --> 00:28:44,480 OF THAT COULD BE INCORPORATED. 760 00:28:44,480 --> 00:28:48,160 THE ISSUE OF THE EARLIER 761 00:28:48,160 --> 00:28:50,160 PREDICTORS OF IMPACT, KEY 762 00:28:50,160 --> 00:28:51,360 CHARACTERISTICS, THESE OTHER 763 00:28:51,360 --> 00:28:53,120 THINGS, BRINGING THOSE FORWARD 764 00:28:53,120 --> 00:28:56,000 IN A WAY THAT CAN BECOME 765 00:28:56,000 --> 00:28:58,920 ESTABLISH AND ACCEPTED TO 766 00:28:58,920 --> 00:29:00,440 SCIENCE IS SOMETHING THAT WILL 767 00:29:00,440 --> 00:29:04,600 TAKE I THINK A LOT OF FOCUSED 768 00:29:04,600 --> 00:29:05,640 ATTENTION WITH OUTSIDE PARTIES, 769 00:29:05,640 --> 00:29:07,680 AND THAT'S A CRITICAL NEED FOR 770 00:29:07,680 --> 00:29:11,720 THE FUTURE I THINK, FOR THESE 771 00:29:11,720 --> 00:29:12,600 BETTER METHODS. 772 00:29:12,600 --> 00:29:15,120 AND WE'RE IN A TIME NOW WHERE 773 00:29:15,120 --> 00:29:17,120 THERE'S A RECOGNITION OF THE 774 00:29:17,120 --> 00:29:19,120 IMPORTANCE OF DOING THIS WITH 775 00:29:19,120 --> 00:29:20,600 THE WORK ON CUMULATIVE RISK 776 00:29:20,600 --> 00:29:24,240 THAT'S GOING ON AT EPA AND OTHER 777 00:29:24,240 --> 00:29:25,320 AGENCIES. 778 00:29:25,320 --> 00:29:26,200 WITH THE EMPHASIS ON 779 00:29:26,200 --> 00:29:28,280 ENVIRONMENTAL JUSTICE AND THE 780 00:29:28,280 --> 00:29:30,120 NEEDS OF COMMUNITIES AND THE NEW 781 00:29:30,120 --> 00:29:31,560 EXECUTIVE ORDERS AND ALL THOSE 782 00:29:31,560 --> 00:29:33,440 INITIATIVES THAT ARE GOING INTO 783 00:29:33,440 --> 00:29:33,640 THAT. 784 00:29:33,640 --> 00:29:36,160 THERE'S A LOT OF MONEY BEING 785 00:29:36,160 --> 00:29:36,800 SPENT THERE. 786 00:29:36,800 --> 00:29:39,200 THERE'S A LOT OF INTENT TO MAKE 787 00:29:39,200 --> 00:29:41,640 A DIFFERENCE, AND WE STILL DON'T 788 00:29:41,640 --> 00:29:43,480 HAVE THE TOOLS TO DO EVERYTHING 789 00:29:43,480 --> 00:29:44,560 THAT NEEDS TO BE DONE. 790 00:29:44,560 --> 00:29:47,760 WE HAVE TOOLS WE CAN USE BUT IT 791 00:29:47,760 --> 00:29:51,720 WOULD BE GOOD IF THOSE COULD 792 00:29:51,720 --> 00:29:54,120 GO -- PEOPLE LIKE TO SAY NEXT 793 00:29:54,120 --> 00:29:57,520 GEN, I DON'T KNOW IF THAT'S 794 00:29:57,520 --> 00:29:59,480 OUTDATED SLANG NOW BUT HOW COULD 795 00:29:59,480 --> 00:30:03,560 WE MAKE GAINS USING SOME OF THE 796 00:30:03,560 --> 00:30:05,520 METHODS PERHAPS THAT YOU ALL ARE 797 00:30:05,520 --> 00:30:07,600 WORKING ON. 798 00:30:07,600 --> 00:30:08,880 AND THEN ALSO -- I'M SURE I'M 799 00:30:08,880 --> 00:30:11,080 OUT OF TIME BUT THE LAST THING I 800 00:30:11,080 --> 00:30:13,400 WANT TO SAY IS THERE ARE ALSO 801 00:30:13,400 --> 00:30:16,040 THE -- WHEN WE THINK ABOUT 802 00:30:16,040 --> 00:30:17,880 ANIMALS, HUMAN POPULATIONS, BUT 803 00:30:17,880 --> 00:30:20,920 ALSO THE ANIMAL POPULATIONS ARE 804 00:30:20,920 --> 00:30:21,600 AFFECTED BY THE CHEMICAL 805 00:30:21,600 --> 00:30:24,360 RELEASES AND SO ON. 806 00:30:24,360 --> 00:30:25,880 AND I INCLUDED THIS SLIDE IN 807 00:30:25,880 --> 00:30:27,600 HERE, I DON'T HAVE TIME TO SHOW 808 00:30:27,600 --> 00:30:32,840 MY SLIDES, I KNOW THAT, FOR 809 00:30:32,840 --> 00:30:36,200 EXAMPLE STUDY ON IMPACTS ON 810 00:30:36,200 --> 00:30:41,000 WHALES, CUMULATIVE EFFECTS, THE 811 00:30:41,000 --> 00:30:43,520 RIGHT WHALE, IT'S GOING EXTINCT, 812 00:30:43,520 --> 00:30:44,160 POPULATIONS ARE DIMINISHING AND 813 00:30:44,160 --> 00:30:45,600 THEY ARE NOT SURE OF THE REASONS 814 00:30:45,600 --> 00:30:47,720 BUT CHEMICALS COULD BE PART OF 815 00:30:47,720 --> 00:30:49,280 IT FOR THAT SPECIES AND FOR 816 00:30:49,280 --> 00:30:52,920 OTHERS, AND SO WHEN WE THINK 817 00:30:52,920 --> 00:30:55,720 ABOUT ANIMAL WELFARE AND 818 00:30:55,720 --> 00:30:59,240 SURVIVAL OF SPECIES, YOU KNOW, 819 00:30:59,240 --> 00:31:04,080 THE CUMULATIVE IMPACT ON -- AT 820 00:31:04,080 --> 00:31:05,920 THE POPULATION LEVEL IS RELEVANT 821 00:31:05,920 --> 00:31:07,720 FOR SPECIES, MAYBE THAT COULD 822 00:31:07,720 --> 00:31:08,880 BECOME A CONCERN THAT WE ALSO 823 00:31:08,880 --> 00:31:12,760 THINK OF WHEN WE'RE WORKING ON 824 00:31:12,760 --> 00:31:13,240 METHODS. 825 00:31:13,240 --> 00:31:16,440 THANK YOU FOR THE OPPORTUNITY TO 826 00:31:16,440 --> 00:31:16,760 SPEAK. 827 00:31:16,760 --> 00:31:20,200 I'M SORRY I WENT OVER BUT I 828 00:31:20,200 --> 00:31:21,360 APPRECIATE IT. 829 00:31:21,360 --> 00:31:21,640 THANK YOU. 830 00:31:21,640 --> 00:31:24,760 >> THANK YOU, DR. KYLE. 831 00:31:24,760 --> 00:31:25,960 THESE ARE REALLY CRITICALLY 832 00:31:25,960 --> 00:31:27,920 IMPORTANT POINTS THAT YOU'RE 833 00:31:27,920 --> 00:31:31,200 MAKING PARTICULARLY IN TERMS OF 834 00:31:31,200 --> 00:31:33,400 COMMUNITY ENGAGEMENT, 835 00:31:33,400 --> 00:31:35,280 UNDERSTANDING CUMULATIVE RISK, 836 00:31:35,280 --> 00:31:36,160 COMMUNICATION, SO REALLY 837 00:31:36,160 --> 00:31:40,840 APPRECIATE YOU JOINING US TODAY 838 00:31:40,840 --> 00:31:41,840 AND GIVING FEEDBACK. 839 00:31:41,840 --> 00:31:44,680 WE'LL POST YOUR SLIDES IN THEIR 840 00:31:44,680 --> 00:31:49,280 ENTIRETY, IF IT'S ALL RIGHT WITH 841 00:31:49,280 --> 00:31:52,280 YOU, ON THE THE ICCVAM SITE AND 842 00:31:52,280 --> 00:31:53,320 WE HAVE FOLLOW-UP MEETINGS NEXT 843 00:31:53,320 --> 00:31:55,440 WEEK TO DISCUSS IN PARTICULAR 844 00:31:55,440 --> 00:31:56,720 THE PUBLIC COMMENTS, WE'LL DIVE 845 00:31:56,720 --> 00:31:59,720 INTO MORE DETAIL IN OUR CLOSED 846 00:31:59,720 --> 00:32:00,360 SESSION. 847 00:32:00,360 --> 00:32:02,320 THANK YOU VERY MUCH. 848 00:32:02,320 --> 00:32:04,840 NEXT PUBLIC COMMENTER IS AMY 849 00:32:04,840 --> 00:32:06,480 CLIPPINGER FROM PETA SCIENCE 850 00:32:06,480 --> 00:32:07,280 CONSORTIUM INTERNATIONAL, HERE 851 00:32:07,280 --> 00:32:08,920 WITH US IN PERSON. 852 00:32:08,920 --> 00:32:12,200 PLEASE MAKE YOUR WAY TO THE 853 00:32:12,200 --> 00:32:12,440 PODIUM. 854 00:32:12,440 --> 00:32:19,240 THANK YOU. 855 00:32:19,240 --> 00:32:20,840 >> THANKS, NICOLE. 856 00:32:20,840 --> 00:32:21,480 THANKS, EVERYBODY, FOR TAKING 857 00:32:21,480 --> 00:32:22,840 THE TIME TO HEAR PUBLIC COMMENTS 858 00:32:22,840 --> 00:32:24,680 THIS MORNING. 859 00:32:24,680 --> 00:32:25,320 I'LL TRY TO BE BRIEF. 860 00:32:25,320 --> 00:32:27,680 AT THE BE ON SET OF THE MEETING, 861 00:32:27,680 --> 00:32:29,880 A COUPLE PEOPLE SAID HOW THIS IS 862 00:32:29,880 --> 00:32:30,480 ONE OF THEIR FAVORITE MEETINGS 863 00:32:30,480 --> 00:32:31,120 OF THE YEAR. 864 00:32:31,120 --> 00:32:33,440 I HAVE TO AGREE, IT'S BEEN NICE 865 00:32:33,440 --> 00:32:34,640 SITTING IN THE AUDIENCE 866 00:32:34,640 --> 00:32:36,600 YESTERDAY AND TODAY, HEARING THE 867 00:32:36,600 --> 00:32:38,320 UPDATES FROM THE AGENCIES AND 868 00:32:38,320 --> 00:32:43,040 GREAT WORK THAT HAS BEEN MADE, 869 00:32:43,040 --> 00:32:44,400 PROGRESS MADE OVER THE PAST 870 00:32:44,400 --> 00:32:44,600 YEAR. 871 00:32:44,600 --> 00:32:46,640 IN PARTICULAR IT'S BEEN NICE TO 872 00:32:46,640 --> 00:32:50,840 SEE THAT EFFORTS HAVE ADDRESSED 873 00:32:50,840 --> 00:32:55,960 THE WHOLE PROGRESS FROM METHOD 874 00:32:55,960 --> 00:32:57,160 DEVELOPMENT THROUGH CONFIDENCE 875 00:32:57,160 --> 00:32:59,280 IN THAT METHOD, DEVELOPING 876 00:32:59,280 --> 00:33:00,240 GUIDANCE, COMMUNICATING WITH 877 00:33:00,240 --> 00:33:01,960 BOTH SCIENTISTS AND AS THE OTHER 878 00:33:01,960 --> 00:33:06,920 AMY JUST POINTED OUT NICELY, 879 00:33:06,920 --> 00:33:08,440 NON-SCIENTISTS AS WELL. 880 00:33:08,440 --> 00:33:12,160 I WAS REALLY HAPPY TO HEAR ABOUT 881 00:33:12,160 --> 00:33:14,240 THE VALIDATION EFFORTS TAKING 882 00:33:14,240 --> 00:33:18,560 PLACE WITHIN BOTH OECD AND 883 00:33:18,560 --> 00:33:18,800 ICCVAM. 884 00:33:18,800 --> 00:33:21,240 THERE'S A REALLY NEED TO UPDATE 885 00:33:21,240 --> 00:33:24,000 THAT 20+ YEAR OLD PROCESS FOR 886 00:33:24,000 --> 00:33:25,080 VALIDATING NEW METHODS SO WE CAN 887 00:33:25,080 --> 00:33:26,880 GET THE BEST SCIENCE OUT, GET 888 00:33:26,880 --> 00:33:29,800 THOSE TOOLS OUT INTO THE HANDS 889 00:33:29,800 --> 00:33:31,440 OF RESEARCHERS, FASTER. 890 00:33:31,440 --> 00:33:33,680 WHILE STILL HOLDING TRUE AND 891 00:33:33,680 --> 00:33:36,320 STICKING TO THOSE PRINCIPLES OF 892 00:33:36,320 --> 00:33:39,320 VALIDATION THAT HOLD TRUE TODAY. 893 00:33:39,320 --> 00:33:41,520 I WAS ALSO HAPPY TO HEAR ABOUT 894 00:33:41,520 --> 00:33:42,920 SOME OF THE GUIDANCE THAT HAS 895 00:33:42,920 --> 00:33:47,160 COME OUT IN THE PAST YEAR AT THE 896 00:33:47,160 --> 00:33:49,040 OECD AND OTHERWISE. 897 00:33:49,040 --> 00:33:50,760 THIS IS SOMETHING THAT'S SO 898 00:33:50,760 --> 00:33:51,720 CRITICALLY IMPORTANT. 899 00:33:51,720 --> 00:33:52,800 I THINK IT'S ONE OF THE FINAL 900 00:33:52,800 --> 00:33:55,600 STEPS BEFORE WE REACH THE FINISH 901 00:33:55,600 --> 00:33:58,440 LINE, AND THERE ARE CERTAINLY 902 00:33:58,440 --> 00:34:01,040 CASES WHERE COMPANIES AREN'T 903 00:34:01,040 --> 00:34:02,920 EITHER AWARE OF THE NAM OR THEY 904 00:34:02,920 --> 00:34:04,280 MIGHT BE AWARE BUT NOT CERTAIN 905 00:34:04,280 --> 00:34:05,480 IT WILL BE ACCEPTED OR WILL IT 906 00:34:05,480 --> 00:34:08,080 BE ACCEPTED IN A TIMELY MANNER, 907 00:34:08,080 --> 00:34:10,360 OR WILL IT BE ACCEPTABLE FOR 908 00:34:10,360 --> 00:34:13,000 THEIR SPECIFIC CONTEXT OF USE, 909 00:34:13,000 --> 00:34:17,480 SO I THINK INCREASING THE AMOUNT 910 00:34:17,480 --> 00:34:18,600 OF COMMUNICATION, GUIDANCE, 911 00:34:18,600 --> 00:34:21,440 WHETHER NAMs CAN BE USED, WHEN 912 00:34:21,440 --> 00:34:23,040 THEY CAN BE USED 913 00:34:23,040 --> 00:34:25,120 IS CRITICALLY IMPORTANT AS ONE 914 00:34:25,120 --> 00:34:26,120 FAMILIAR PELL, SUZIE TALKED 915 00:34:26,120 --> 00:34:30,280 ABOUT THE GREAT WORK THAT THE 916 00:34:30,280 --> 00:34:39,680 FDA DID TO REVIEW RODENT AND DOG 917 00:34:39,680 --> 00:34:39,920 STUDIES. 918 00:34:39,920 --> 00:34:43,520 AND THAT STRIKES ME, WE WANT TO 919 00:34:43,520 --> 00:34:44,080 MAKE SURE THE REGULATED 920 00:34:44,080 --> 00:34:51,840 COMMUNITY KNOWS THAT AS QUICKLY 921 00:34:51,840 --> 00:34:52,920 AS POSSIBLE. 922 00:34:52,920 --> 00:34:54,920 I WILL LEAVE IT AT THAT. 923 00:34:54,920 --> 00:34:55,440 THANKS AGAIN, EVERYBODY. 924 00:34:55,440 --> 00:35:00,480 LOOKING FORWARD TO DOING THIS 925 00:35:00,480 --> 00:35:00,760 NEXT YEAR. 926 00:35:00,760 --> 00:35:10,960 [APPLAUSE] 927 00:35:19,360 --> 00:35:21,800 >> NEXT IS ELIZABETH BAKER, 928 00:35:21,800 --> 00:35:23,120 PHYSICIANS COMMITTEE FOR 929 00:35:23,120 --> 00:35:23,720 RESPONSIBLE MEDICINE. 930 00:35:23,720 --> 00:35:24,880 >> HELLO TO EVERYONE. 931 00:35:24,880 --> 00:35:25,960 I REGRET NOT BEING ABLE TO BE 932 00:35:25,960 --> 00:35:31,120 THERE IN PERSON TO SEE YOU ALL, 933 00:35:31,120 --> 00:35:32,680 BUT APPRECIATE THE ABILITY TO 934 00:35:32,680 --> 00:35:34,760 PARTICIPATE FROM A AFAR. 935 00:35:34,760 --> 00:35:36,680 I WANT TO ECHO WHAT DB 936 00:35:36,680 --> 00:35:38,160 CLIPPINGER SAID AND MANY OTHERS 937 00:35:38,160 --> 00:35:41,320 THAT I LOOK FORWARD TO THIS 938 00:35:41,320 --> 00:35:42,960 FORUM HEARING EVERYONE'S 939 00:35:42,960 --> 00:35:43,920 UPDATES. 940 00:35:43,920 --> 00:35:45,240 THE PRESENTATIONS HAVE 941 00:35:45,240 --> 00:35:46,680 DEMONSTRATED COMMITMENT TO 942 00:35:46,680 --> 00:35:48,080 INTEGRATING TESTING STRATEGIES 943 00:35:48,080 --> 00:35:49,880 THAT PROTECT HUMAN HEALTH AND 944 00:35:49,880 --> 00:35:52,160 THE ENVIRONMENT WHILE REPLACING 945 00:35:52,160 --> 00:35:53,800 AND REDUCING ANIMAL USE. 946 00:35:53,800 --> 00:35:55,720 IT'S CLEAR NICEATM AND ICCVAM 947 00:35:55,720 --> 00:35:57,640 ARE DOING THE HARD AND NECESSARY 948 00:35:57,640 --> 00:35:59,680 WORK TO ADVANCE SCIENCE. 949 00:35:59,680 --> 00:36:00,760 THANK YOU FOR THAT. 950 00:36:00,760 --> 00:36:02,000 MY COMMENTS ARE DEVELOPED WITH 951 00:36:02,000 --> 00:36:04,520 THE HELP OF OUR TEAM AT 952 00:36:04,520 --> 00:36:07,560 PHYSICIANS COMMITTEE. 953 00:36:07,560 --> 00:36:11,000 JESSICA PONDER, JOHN, ERIN, AND 954 00:36:11,000 --> 00:36:13,160 EMILY ANDERSON, AND WRITTEN 955 00:36:13,160 --> 00:36:14,480 COMMENTS ARE DIFFERENT SO I 956 00:36:14,480 --> 00:36:17,000 ENCOURAGE PEOPLE TO TAKE A LOOK 957 00:36:17,000 --> 00:36:19,520 AT THOSE AS WELL. 958 00:36:19,520 --> 00:36:20,480 ONE THING I REALLY APPRECIATE 959 00:36:20,480 --> 00:36:24,920 ABOUT THE FORUM WE SHARE IDEAS 960 00:36:24,920 --> 00:36:26,760 TO COMPLEMENT THE GREAT WORK 961 00:36:26,760 --> 00:36:28,880 BEING ACCOMPLISHED ALREADY. 962 00:36:28,880 --> 00:36:31,520 I THINK THAT WE'VE ALL COME TO 963 00:36:31,520 --> 00:36:32,920 UNDERSTAND THAT DEVELOPING AND 964 00:36:32,920 --> 00:36:34,960 EVALUATING SCIENCE IS JUST ONE 965 00:36:34,960 --> 00:36:37,960 IMPORTANT FACTOR IN ADVANCING 966 00:36:37,960 --> 00:36:39,040 NEW APPROACHES, BUT ALSO 967 00:36:39,040 --> 00:36:41,440 POLICIES MUST ADVANCE, TRAINING 968 00:36:41,440 --> 00:36:42,200 AND EDUCATIONAL OPPORTUNITIES 969 00:36:42,200 --> 00:36:44,400 ARE REALLY IMPORTANT AS WELL. 970 00:36:44,400 --> 00:36:47,360 SO I'D LIKE TO THANK DR. GORDON 971 00:36:47,360 --> 00:36:49,000 FOR HIS COMMENTS YESTERDAY ON 972 00:36:49,000 --> 00:36:51,600 THE NEED FOR AGENCIES TO TAKE A 973 00:36:51,600 --> 00:36:52,600 LEADING ROLE IN COMMUNICATING 974 00:36:52,600 --> 00:36:55,680 WHEN AND HOW NAMs CAN BE USED. 975 00:36:55,680 --> 00:36:56,520 WE CONSISTENTLY HEAR FROM 976 00:36:56,520 --> 00:36:58,400 COMPANIES THAT THEY KNOW HOW TO 977 00:36:58,400 --> 00:37:00,520 USE ANIMALS AND THAT CAN IT BE 978 00:37:00,520 --> 00:37:02,800 HARD TO MAKE A CASE FOR USING 979 00:37:02,800 --> 00:37:05,840 NAMs WITHOUT THE VERY CLEAR 980 00:37:05,840 --> 00:37:07,160 COMMUNICATION REGARDING 981 00:37:07,160 --> 00:37:07,480 ACCEPTANCE. 982 00:37:07,480 --> 00:37:09,160 AND EVERY AGENCY THAT HAS 983 00:37:09,160 --> 00:37:10,920 PRESENTED IS DOING GREAT WORK TO 984 00:37:10,920 --> 00:37:14,280 ADVANCE NAMs, AND SO I HOPE 985 00:37:14,280 --> 00:37:16,000 THAT AGENCIES WILL VIEW UPDATING 986 00:37:16,000 --> 00:37:18,560 THEIR OWN POLICIES TO CLEARLY 987 00:37:18,560 --> 00:37:19,720 REFLECT NAM ACCEPTANCE AS 988 00:37:19,720 --> 00:37:21,400 COMPLEMENTARY TO ALL THE OTHER 989 00:37:21,400 --> 00:37:24,640 GREAT WORK THAT IS HAPPENING. 990 00:37:24,640 --> 00:37:27,720 ALONG THOSE LINES WE APPRECIATE 991 00:37:27,720 --> 00:37:31,120 THE MANY EFFORTS BY ICCVAM AND 992 00:37:31,120 --> 00:37:32,880 NICEATM STAFF TO INTEGRATE 993 00:37:32,880 --> 00:37:34,520 METHODS AND REDUCE ANIMAL USE 994 00:37:34,520 --> 00:37:35,800 THROUGH PARTICIPATION AT THE 995 00:37:35,800 --> 00:37:37,720 OECD, STAFF ARE PARTICULARLY 996 00:37:37,720 --> 00:37:43,160 EXCITED ABOUT THE COLLABORATION 997 00:37:43,160 --> 00:37:44,040 TO DEVELOP AOP AND PRIORITIZE -- 998 00:37:44,040 --> 00:37:48,280 I HAVE A PROBLEM WITH THIS WORD, 999 00:37:48,280 --> 00:37:50,920 EPIDEMIOLOGICAL DATA, WEIGHT OF 1000 00:37:50,920 --> 00:37:52,480 EVIDENCE APPROACH TO DEFINING 1001 00:37:52,480 --> 00:37:53,640 RESPIRATORY SENSITIZERS BASED ON 1002 00:37:53,640 --> 00:37:54,000 HUMANS. 1003 00:37:54,000 --> 00:37:57,280 THIS IS A REALLY STRONG EXAMPLE 1004 00:37:57,280 --> 00:38:01,080 OF NEGATIVE EFFECT IN HUMANS NOT 1005 00:38:01,080 --> 00:38:02,520 OBSERVED IN ANIMALS SO WE 1006 00:38:02,520 --> 00:38:03,920 APPRECIATE OECD SUPPORTING THIS 1007 00:38:03,920 --> 00:38:05,560 EFFORT TO PRIORITIZE AND 1008 00:38:05,560 --> 00:38:07,120 IMPLEMENT NAMs, AND OUR STAFF 1009 00:38:07,120 --> 00:38:08,880 ARE LOOKING FORWARD TO 1010 00:38:08,880 --> 00:38:11,720 COLLABORATING ON THE UPCOMING 1011 00:38:11,720 --> 00:38:13,040 DETAILED REVIEW PAPER. 1012 00:38:13,040 --> 00:38:14,560 IN TERMS OF VALIDATION, 1013 00:38:14,560 --> 00:38:15,240 QUALIFICATION, EVALUATION, 1014 00:38:15,240 --> 00:38:16,760 WHATEVER YOU CALL IT, I'M 1015 00:38:16,760 --> 00:38:18,400 NOTICING A THEME. 1016 00:38:18,400 --> 00:38:20,800 THAT IS THAT MORE AND MORE 1017 00:38:20,800 --> 00:38:22,320 ORGANIZATIONS ARE LOOKING TO 1018 00:38:22,320 --> 00:38:25,200 UNDERSTAND THE CAPABILITIES AND 1019 00:38:25,200 --> 00:38:26,400 EVEN LIMITATIONS OF EXISTING 1020 00:38:26,400 --> 00:38:26,840 METHODS. 1021 00:38:26,840 --> 00:38:30,240 NICEATM HAS DONE A REALLY GREAT 1022 00:38:30,240 --> 00:38:31,680 JOB CHAMPIONING SCIENTIFICALLY 1023 00:38:31,680 --> 00:38:32,800 SOUND AND OBJECTIVE EVALUATION 1024 00:38:32,800 --> 00:38:37,560 OF NOT ONLY IN VITRO AND IN 1025 00:38:37,560 --> 00:38:41,400 SILICO METHODS BUT ALSO IN VIVO 1026 00:38:41,400 --> 00:38:45,560 METHODS ADOPTED BEFORE FORMAL 1027 00:38:45,560 --> 00:38:46,320 VALIDATION PROCESSES WERE 1028 00:38:46,320 --> 00:38:46,600 ESTABLISHED. 1029 00:38:46,600 --> 00:38:47,640 EPA AND OTHERS ARE DOING THIS 1030 00:38:47,640 --> 00:38:50,400 WORK AND WE THINK IT'S IMPORTANT 1031 00:38:50,400 --> 00:38:53,920 FOR HUMAN-SPECIFIC NAMs TO BE 1032 00:38:53,920 --> 00:38:56,840 EVALUATED USING HUMAN 1033 00:38:56,840 --> 00:38:59,800 INFORMATION WHEREVER POSSIBLE. 1034 00:38:59,800 --> 00:39:02,520 I'VE NOTICED SOME ARE VIEWING 1035 00:39:02,520 --> 00:39:04,280 NAMs AS POTENTIAL TO FILL 1036 00:39:04,280 --> 00:39:07,240 GAPS, AND WHILE THAT IS A 1037 00:39:07,240 --> 00:39:08,440 BENEFIT OF NAMs, I THINK IT'S 1038 00:39:08,440 --> 00:39:11,720 IMPORTANT, I THINK WE ALSO NEED 1039 00:39:11,720 --> 00:39:13,800 TO KEEP IN MIND THAT WE ALSO 1040 00:39:13,800 --> 00:39:15,680 NEED TO IMPROVE EXISTING TESTING 1041 00:39:15,680 --> 00:39:18,760 AND REDUCE ANIMAL USE. 1042 00:39:18,760 --> 00:39:22,000 SO JUST I GUESS A COMMENT TO BE 1043 00:39:22,000 --> 00:39:23,560 MORE BROAD AND HOW WE'RE 1044 00:39:23,560 --> 00:39:26,960 THINKING ABOUT NAMs AND NOT 1045 00:39:26,960 --> 00:39:29,440 JUST AS GAP FILLERS. 1046 00:39:29,440 --> 00:39:30,080 MULTIPLE PRESENTERS INCLUDED 1047 00:39:30,080 --> 00:39:31,960 METRICS AS PART OF THEIR NAMs 1048 00:39:31,960 --> 00:39:33,400 WORK, AND I HAVE SAID THIS 1049 00:39:33,400 --> 00:39:34,600 BEFORE, I DON'T THINK IT'S BEEN 1050 00:39:34,600 --> 00:39:36,040 VERY WELL RECEIVED BUT I DO 1051 00:39:36,040 --> 00:39:38,440 THINK IT'S IMPORTANT SO I'LL SAY 1052 00:39:38,440 --> 00:39:39,320 IT AGAIN. 1053 00:39:39,320 --> 00:39:40,760 WE REALLY DON'T KNOW HOW MANY 1054 00:39:40,760 --> 00:39:42,880 ANIMALS ARE USED IN TESTING. 1055 00:39:42,880 --> 00:39:44,600 AND I THINK A LOT OF US ARE HERE 1056 00:39:44,600 --> 00:39:47,000 BECAUSE WE WANT TO ADVANCE NEW 1057 00:39:47,000 --> 00:39:48,720 APPROACHES, WE ALSO WANT TO HELP 1058 00:39:48,720 --> 00:39:49,480 REDUCE ANIMAL USE. 1059 00:39:49,480 --> 00:39:52,240 AND IF WE'RE GOING TO REDUCE 1060 00:39:52,240 --> 00:39:54,080 ANIMAL USE, WE NEED TO 1061 00:39:54,080 --> 00:39:55,360 UNDERSTAND AND KNOW HOW TO 1062 00:39:55,360 --> 00:39:55,960 MEASURE IT. 1063 00:39:55,960 --> 00:39:58,160 I HAVE A REALLY HARD TIME 1064 00:39:58,160 --> 00:39:59,800 UNDERSTANDING HOW WE CAN MEASURE 1065 00:39:59,800 --> 00:40:02,200 PROGRESS IF WE DON'T HAVE A 1066 00:40:02,200 --> 00:40:04,680 BASELINE, AND SO I KNOW IT'S NOT 1067 00:40:04,680 --> 00:40:06,680 AN EASY ISSUE, AND THAT THERE 1068 00:40:06,680 --> 00:40:08,200 ARE INHERENT CHALLENGES AROUND 1069 00:40:08,200 --> 00:40:10,600 COLLECTING AND REPORTING THIS 1070 00:40:10,600 --> 00:40:11,200 INFORMATION. 1071 00:40:11,200 --> 00:40:12,240 BUT I DO THINK THAT SOME 1072 00:40:12,240 --> 00:40:15,520 PROGRESS COULD BE MADE WITH 1073 00:40:15,520 --> 00:40:17,480 AGENCY LEADERSHIP, AND SO WE 1074 00:40:17,480 --> 00:40:20,320 THINK ONE -- A GOOD START WOULD 1075 00:40:20,320 --> 00:40:21,880 BE FOR ICCVAM AGENCIES TO START 1076 00:40:21,880 --> 00:40:25,280 TRACKING THE NUMBER OF ANIMALS 1077 00:40:25,280 --> 00:40:27,120 SUBMITTED BY SPECIES TEST AND 1078 00:40:27,120 --> 00:40:29,400 ENDPOINT AND MAKE THESE PUBLICLY 1079 00:40:29,400 --> 00:40:29,960 AVAILABLE. 1080 00:40:29,960 --> 00:40:33,800 SO WE KNOW IT WON'T COVER ALL 1081 00:40:33,800 --> 00:40:38,720 ANIMALS USED BUT THINK IT WOULD 1082 00:40:38,720 --> 00:40:40,360 BE A GOOD START. 1083 00:40:40,360 --> 00:40:42,240 I WANTED TO COMMENT ON QUESTION 1084 00:40:42,240 --> 00:40:44,640 DR. KYLE ASKED AND EXPANDED UPON 1085 00:40:44,640 --> 00:40:47,240 TODAY THAT WAS VERY INSIGHTFUL 1086 00:40:47,240 --> 00:40:49,760 ABOUT THE IMPORTANT 1087 00:40:49,760 --> 00:40:50,640 OPPORTUNITIES -- AN UPON 1088 00:40:50,640 --> 00:40:51,400 OPPORTUNITY FOR NAMs, THAT'S 1089 00:40:51,400 --> 00:40:53,360 THE OPPORTUNITY TO DEVELOP 1090 00:40:53,360 --> 00:40:55,920 NAMs TO ADDRESS CO-EXPOSURES 1091 00:40:55,920 --> 00:40:57,320 TO PESTICIDES. 1092 00:40:57,320 --> 00:40:59,760 THIS IS A MAJOR REAL WORLD 1093 00:40:59,760 --> 00:41:00,760 CONCERN AND ENVIRONMENTAL 1094 00:41:00,760 --> 00:41:04,560 JUSTICE, AS FARM WORKERS AND 1095 00:41:04,560 --> 00:41:05,760 FAMILIES AS WELL AS COMMUNITIES 1096 00:41:05,760 --> 00:41:08,040 ARE NOT EXPOSED TO PESTICIDE 1097 00:41:08,040 --> 00:41:10,240 MIXTURES OR FORMULATIONS ONE AT 1098 00:41:10,240 --> 00:41:12,400 A TIME BUT RATHER CHRONICALLY 1099 00:41:12,400 --> 00:41:14,640 OVER THE COURSE OF A LIFETIME. 1100 00:41:14,640 --> 00:41:16,400 SOMETIMES EVEN STARTING IN 1101 00:41:16,400 --> 00:41:18,360 GESTATION. 1102 00:41:18,360 --> 00:41:21,880 SO WE'D LIKE TO SUGGEST THAT THE 1103 00:41:21,880 --> 00:41:24,360 EPA ENGAGE PESTICIDE PROGRAM 1104 00:41:24,360 --> 00:41:25,880 DIALOGUE COMMITTEE TO PRIORITIZE 1105 00:41:25,880 --> 00:41:32,560 DEVELOPMENT OF NAMs THAT CAN 1106 00:41:32,560 --> 00:41:33,440 ASSESS EPIGENETIC EFFECTS 1107 00:41:33,440 --> 00:41:35,760 CHRONIC EXPOSURES AS PART OF THE 1108 00:41:35,760 --> 00:41:46,320 CHANCE TO ADVANCE ENVIRONMENTAL 1109 00:42:10,520 --> 00:42:15,680 JUSTICE. 1110 00:42:15,680 --> 00:42:15,960 THAT'S IT. 1111 00:42:15,960 --> 00:42:20,240 >> NEXT IS RANDOLPH ASHTON FROM 1112 00:42:20,240 --> 00:42:21,040 NEUROSETTA. 1113 00:42:21,040 --> 00:42:22,280 DO YOU HAVE SLIDES? 1114 00:42:22,280 --> 00:42:22,520 >>YES. 1115 00:42:22,520 --> 00:42:25,480 >> ARE YOU LOOKING AT MY SLIDE 1116 00:42:25,480 --> 00:42:25,680 SHOW? 1117 00:42:25,680 --> 00:42:27,840 >> THANKS VERY MUCH. 1118 00:42:27,840 --> 00:42:28,160 >> AWESOME. 1119 00:42:28,160 --> 00:42:29,720 THANK YOU. 1120 00:42:29,720 --> 00:42:32,800 GOOD MORNING FROM WISCONSIN THIS 1121 00:42:32,800 --> 00:42:34,680 TIME OF YEAR. 1122 00:42:34,680 --> 00:42:37,520 I'M RANDOLPH ASHTON, ASSOCIATE 1123 00:42:37,520 --> 00:42:39,960 PROFESSOR OF BIOMEDICAL 1124 00:42:39,960 --> 00:42:40,760 ENGINEERING AT UNIVERSITY OF 1125 00:42:40,760 --> 00:42:41,480 WISCONSIN-MADISON. 1126 00:42:41,480 --> 00:42:44,640 MY LAB OVER THE LAST COUPLE 1127 00:42:44,640 --> 00:42:48,120 PANDEMIC YEARS DECIDED TO DO A 1128 00:42:48,120 --> 00:42:49,440 START-UP, STUCK AT HOME, 1129 00:42:49,440 --> 00:42:52,160 TECHNOLOGY FUNDED BY THE EPA, 1130 00:42:52,160 --> 00:42:53,920 NOW BY NIEHS, AND IT'S SOMETHING 1131 00:42:53,920 --> 00:43:04,320 THAT'S BEEN GEARED FOR 1132 00:43:13,840 --> 00:43:14,200 REGULATORY. 1133 00:43:14,200 --> 00:43:17,600 ONE WOULD LIKE THE CHANCE TO USE 1134 00:43:17,600 --> 00:43:19,640 I'M EMBRYOS, BUT YOU CAN'T, A 1135 00:43:19,640 --> 00:43:20,200 CRITICAL POINT OF HUMAN 1136 00:43:20,200 --> 00:43:21,960 DEVELOPMENT. 1137 00:43:21,960 --> 00:43:25,440 IN THE LAST COUPLE DECADES THE 1138 00:43:25,440 --> 00:43:28,640 USE OF HUMAN STEM CELLS DERIVED 1139 00:43:28,640 --> 00:43:33,120 FROM PATIENTS, AND YOU CAN GUIDE 1140 00:43:33,120 --> 00:43:35,640 THEM DOWN THE NEURAL 1141 00:43:35,640 --> 00:43:37,080 DIFFERENTIAL CHANGES, THEY 1142 00:43:37,080 --> 00:43:41,880 RECAPITULATE ASPECTS OF HUMAN 1143 00:43:41,880 --> 00:43:42,880 CENTRAL NERVOUS SYSTEM 1144 00:43:42,880 --> 00:43:44,520 DEVELOPMENT, THE TOOL HAS 1145 00:43:44,520 --> 00:43:45,840 LIMITATIONS IN THE 1146 00:43:45,840 --> 00:43:47,160 REPRODUCIBILITY OF THE SYSTEM, 1147 00:43:47,160 --> 00:43:49,560 AND THE ABILITY TO ANALYZE 1148 00:43:49,560 --> 00:43:51,280 WHAT'S GOING ON INSIDE THESE 1149 00:43:51,280 --> 00:43:53,800 TISSUES WHICH CAN BE MILLIMETERS 1150 00:43:53,800 --> 00:43:54,240 IN SIZE. 1151 00:43:54,240 --> 00:44:01,480 AND SO WHAT WE'VE DONE AT IS 1152 00:44:01,480 --> 00:44:02,600 NEUROSETTA IS BIOLOGICALLY 1153 00:44:02,600 --> 00:44:04,160 ENGINEERED INTO A 1154 00:44:04,160 --> 00:44:04,840 HIGH-THROUGHPUT SYSTEM. 1155 00:44:04,840 --> 00:44:06,720 IF YOU'RE LOOKING AT EARLY HUMAN 1156 00:44:06,720 --> 00:44:08,480 DEVELOPMENT, SIMILAR TO A CHICK, 1157 00:44:08,480 --> 00:44:11,720 TOP-DOWN ON THE CHICK EMBRYO, 1158 00:44:11,720 --> 00:44:14,080 NEURAL TUBE FORMS, HEAD REGION, 1159 00:44:14,080 --> 00:44:15,400 THROUGH THE SPINAL CORD, 1160 00:44:15,400 --> 00:44:17,480 TRANSVERSE SLICE HEAD-ON YOU CAN 1161 00:44:17,480 --> 00:44:19,720 SEE THE NEURAL TUBE STRUCTURE. 1162 00:44:19,720 --> 00:44:21,360 THIS STRUCTURE IS COMPOSED OF 1163 00:44:21,360 --> 00:44:22,920 NEURAL STEM CELLS AND THIS IS 1164 00:44:22,920 --> 00:44:26,080 WHAT ALL TISSUES OF THE BRAIN, 1165 00:44:26,080 --> 00:44:27,880 RETINA AND SPINAL CORD ARE 1166 00:44:27,880 --> 00:44:29,800 DERIVED FROM. 1167 00:44:29,800 --> 00:44:34,600 AND WHEN YOU DIFFERENTIATE 1168 00:44:34,600 --> 00:44:36,320 PLURIPOTENT STEM CELLS, THE STEM 1169 00:44:36,320 --> 00:44:37,920 CELLS, THE FIRST CELL TYPE YOU 1170 00:44:37,920 --> 00:44:40,480 GET TO, THEY ARE PROGRAMMED TO 1171 00:44:40,480 --> 00:44:47,920 UNDERGO THIS NEURAL TUBE TYPE 1172 00:44:47,920 --> 00:44:52,080 MORPHOGENESIS, NEARLY ROSETTES 1173 00:44:52,080 --> 00:44:54,560 FORM IN AN UNCONTROLLED MANNER, 1174 00:44:54,560 --> 00:44:56,360 YOU LOSE CONTROL OF CULTURE OF 1175 00:44:56,360 --> 00:44:59,520 MULTIPLE FORMING IN AN EMBRYO, 1176 00:44:59,520 --> 00:45:01,400 EMBRYONIC LETHAL DEFECT. 1177 00:45:01,400 --> 00:45:04,880 WE ASKED HOW CAN YOU GENERATE 1178 00:45:04,880 --> 00:45:05,640 SINGLE ROSETTES? 1179 00:45:05,640 --> 00:45:09,560 IS SOMEBODY TRYING TO ASK A 1180 00:45:09,560 --> 00:45:10,200 QUESTION? 1181 00:45:10,200 --> 00:45:13,280 NO, OKAY. 1182 00:45:13,280 --> 00:45:20,400 WE'VE INTEGRATED WITH 1183 00:45:20,400 --> 00:45:22,280 SUBSTRATES, THINK OF CULTURAL 1184 00:45:22,280 --> 00:45:24,320 ENGINEERED, IF YOU GET THOSE 1185 00:45:24,320 --> 00:45:28,840 DIMENSIONS JUST RIGHT IN SHAPE 1186 00:45:28,840 --> 00:45:35,520 AND SIZE, YOU CAN INDUCE 1187 00:45:35,520 --> 00:45:36,800 AGGREGATE OF HUMAN PLURIPOTENT 1188 00:45:36,800 --> 00:45:40,080 STEM CELLS AND FORM ROSETTE 1189 00:45:40,080 --> 00:45:41,560 STRUCTURES, THREE DIMENSIONAL, 1190 00:45:41,560 --> 00:45:43,840 RED IS NEURAL STEM CELL MARKER, 1191 00:45:43,840 --> 00:45:49,000 BLUE IS NUCLEI, GREEN IS A 1192 00:45:49,000 --> 00:45:50,200 PROTEIN THAT GETS POLARIZED TO 1193 00:45:50,200 --> 00:45:51,320 THE CENTRAL REGION, YOU'LL SEE 1194 00:45:51,320 --> 00:45:55,160 AS WE GO THROUGH YOU CAN SEE THE 1195 00:45:55,160 --> 00:45:56,000 POLARIZED ROSETTE STRUCTURE IN 1196 00:45:56,000 --> 00:46:01,480 THE MIDDLE OF THE 3D TISSUE. 1197 00:46:01,480 --> 00:46:03,120 WE HAVE HUNDREDS OF THESE IN A 1198 00:46:03,120 --> 00:46:04,600 SINGLE WELL BECAUSE WE HAVE 1199 00:46:04,600 --> 00:46:09,800 ENGINEERED SURFACE TO INSTRUCT 1200 00:46:09,800 --> 00:46:10,720 THIS FORMATION PROCESS. 1201 00:46:10,720 --> 00:46:13,440 WE WORK ON TRYING TO GENERATE 1202 00:46:13,440 --> 00:46:14,600 NEURAL STEM CELLS ACROSS THE 1203 00:46:14,600 --> 00:46:16,640 REGION OF THE DEVELOPING CENTRAL 1204 00:46:16,640 --> 00:46:18,960 NERVOUS SYSTEM SO WE CAN 1205 00:46:18,960 --> 00:46:20,480 GENERATE NEURAL STEM CELLS FROM 1206 00:46:20,480 --> 00:46:21,160 FOREBRAIN THROUGH SPINAL CORD, 1207 00:46:21,160 --> 00:46:23,000 THIS IS ONE OF THE ADVANTAGES OF 1208 00:46:23,000 --> 00:46:24,000 THE SYSTEM. 1209 00:46:24,000 --> 00:46:27,920 YOU CANNOT JUST PROBE FORE BRAIN 1210 00:46:27,920 --> 00:46:29,560 BUT ALL THE WAY THROUGH THE 1211 00:46:29,560 --> 00:46:31,120 DEVELOPING NEURAL TUBE. 1212 00:46:31,120 --> 00:46:32,760 WE COLLABORATE WITH COMPUTER 1213 00:46:32,760 --> 00:46:34,480 VISION EXPERTS TO CREATE 1214 00:46:34,480 --> 00:46:35,560 HIGH-THROUGHPUT IMAGE ANALYSIS 1215 00:46:35,560 --> 00:46:37,800 OFT WARE, SO THAT WHEN YOU 1216 00:46:37,800 --> 00:46:40,520 COLLECT THESE IMAGES YOU CAN RUN 1217 00:46:40,520 --> 00:46:42,360 IT THROUGH A PIPELINE THAT 1218 00:46:42,360 --> 00:46:46,080 COUNTS THE NUMBER OF ROSETTES 1219 00:46:46,080 --> 00:46:47,960 AND TISSUES, SINGLE ROSETTE 1220 00:46:47,960 --> 00:46:49,680 STRUCTURE, AGAIN AN IN VITRO 1221 00:46:49,680 --> 00:46:51,640 ANALOG TO NEURAL TUBE FORMATION. 1222 00:46:51,640 --> 00:46:54,080 AND SO IF COMBINE THIS YOU CAN 1223 00:46:54,080 --> 00:46:58,520 MAKE A WELL PLATE ASSAY, ROSETTE 1224 00:46:58,520 --> 00:47:00,720 AWAY, PATTERN TO THE LED TO TAIL 1225 00:47:00,720 --> 00:47:01,920 REGIONS OF THE DEVELOPING 1226 00:47:01,920 --> 00:47:03,120 CENTRAL NERVOUS SYSTEM IN ORDER 1227 00:47:03,120 --> 00:47:06,440 TO PROBE OR HAVE ASSAY WHERE YOU 1228 00:47:06,440 --> 00:47:09,160 CAN PROBE HOW CHEMICALS AND 1229 00:47:09,160 --> 00:47:10,720 GENETIC MUTATION WILL AFFECT 1230 00:47:10,720 --> 00:47:11,680 THIS PROCESS. 1231 00:47:11,680 --> 00:47:18,040 SO WE HAVE MADE THIS AN OFF THE 1232 00:47:18,040 --> 00:47:19,240 SHELF ASSAY, CRYOPRESERVE BANKS 1233 00:47:19,240 --> 00:47:21,240 OF CELLS AND FOLLOW THIS 1234 00:47:21,240 --> 00:47:28,480 DIRECTLY INTO OUR MICROPATTERN 1235 00:47:28,480 --> 00:47:31,320 CULTURE SUBSTRATE, 5 TO 7 DAY 1236 00:47:31,320 --> 00:47:35,720 CULTURE PERIOD, AT THE END 1237 00:47:35,720 --> 00:47:37,680 SINGLE IMMUNOCYTO CHEMICAL 1238 00:47:37,680 --> 00:47:38,680 STAINING, IMAGING WITH A 1239 00:47:38,680 --> 00:47:40,080 MICROSCOPE AND FROM THAT SINGLE 1240 00:47:40,080 --> 00:47:45,880 IMAGE YOU CAN GET DATA ON CELL 1241 00:47:45,880 --> 00:47:48,200 VIABILITY, PROLIFERATION, NEURAL 1242 00:47:48,200 --> 00:47:57,560 DIVERSITY, EQUITY, 1243 00:47:57,560 --> 00:47:58,360 -- NEURAL 1244 00:47:58,360 --> 00:47:59,080 DIFFERENTIATION, AND MORPHOGEN 1245 00:47:59,080 --> 00:48:02,640 SIS, THIS IS A SENSITIVE METRIC. 1246 00:48:02,640 --> 00:48:05,480 IN PRACTICE WE CAN TAKE OUR 1247 00:48:05,480 --> 00:48:08,320 CRYOPRESERVED CELLS, SEED THEM 1248 00:48:08,320 --> 00:48:09,760 INTO OUR ROSETTE ARRAY PLATES 1249 00:48:09,760 --> 00:48:12,920 WHICH WE MANUFACTURE AT THE 1250 00:48:12,920 --> 00:48:14,440 UNIVERSITY AND THEN GROW OUR 1251 00:48:14,440 --> 00:48:16,520 ROSETTES IN THE PRESENCE OR 1252 00:48:16,520 --> 00:48:18,440 ABSENCE OF CHEMICALS IN EACH 1253 00:48:18,440 --> 00:48:21,760 WELL OF A 96 WELL PLATE, FROM 1254 00:48:21,760 --> 00:48:23,720 100 TO 500 TISSUE IN THE FORE 1255 00:48:23,720 --> 00:48:27,800 BRAIN THROUGH SPINAL CORD, YOU 1256 00:48:27,800 --> 00:48:30,640 CAN USE ADAPTIVE CONFOCAL 1257 00:48:30,640 --> 00:48:33,480 IMAGING TO COLLECT, TYPICALLY 40 1258 00:48:33,480 --> 00:48:35,200 TO 50 PER WELL, 4,000 PER PLATE, 1259 00:48:35,200 --> 00:48:37,200 RUN THROUGH SOFTWARE THAT WE 1260 00:48:37,200 --> 00:48:38,600 HAVE, CONTINUING TO UPDATE TO 1261 00:48:38,600 --> 00:48:41,120 MAKE IT A.I. NOW. 1262 00:48:41,120 --> 00:48:45,760 AND FROM THAT YOU CAN GET VERY 1263 00:48:45,760 --> 00:48:46,600 NICE DOSE-RESPONSE CURVES, 1264 00:48:46,600 --> 00:48:48,960 PROLIFERATION IS A NUMBER OF 1265 00:48:48,960 --> 00:48:50,840 CELLS PER TISSUE, NEURAL 1266 00:48:50,840 --> 00:48:54,160 DIFFERENTIAL RATE IS A NEURAL 1267 00:48:54,160 --> 00:48:56,320 EPIDERMAL DETERMINANT FOR NEURAL 1268 00:48:56,320 --> 00:48:59,000 STEM CELLS AND ROSETTE FORMATION 1269 00:48:59,000 --> 00:48:59,240 METRIC. 1270 00:48:59,240 --> 00:49:03,320 AS YOU CAN SEE HERE FOR KNOWN 1271 00:49:03,320 --> 00:49:06,080 DEVELOPMENTAL NEUROTOXIC 1272 00:49:06,080 --> 00:49:08,400 CHEMICAL METHOTREXATE, THE MOST 1273 00:49:08,400 --> 00:49:09,080 SENSITIVE. 1274 00:49:09,080 --> 00:49:10,560 THE JUXTAPOSITION OF THESE 1275 00:49:10,560 --> 00:49:11,760 CURVES CHANGES BASED ON 1276 00:49:11,760 --> 00:49:14,320 CHEMICALS AND WHICH PATHWAYS 1277 00:49:14,320 --> 00:49:15,400 THEY ARE AFFECTING, THAT 1278 00:49:15,400 --> 00:49:16,920 DIFFERENCE IN POSITION TELLS YOU 1279 00:49:16,920 --> 00:49:20,560 NOT JUST WHETHER SOMETHING IS 1280 00:49:20,560 --> 00:49:24,680 TOXICS BUT GIVES MECHANISTIC 1281 00:49:24,680 --> 00:49:26,560 INSIGHT INTO WHAT PATHWAYS ARE 1282 00:49:26,560 --> 00:49:27,760 BEING AFFECTED BY THOSE 1283 00:49:27,760 --> 00:49:29,040 CHEMICALS. 1284 00:49:29,040 --> 00:49:30,720 IF YOU LOOK AT STANDARD 1285 00:49:30,720 --> 00:49:32,360 SCREENING BATTERY, A NUMBER OF 1286 00:49:32,360 --> 00:49:34,520 ASSAYS, THIS IS COMING FROM 1287 00:49:34,520 --> 00:49:35,640 RECENT PUBLICATIONS, THERE ARE 1288 00:49:35,640 --> 00:49:38,880 MORE OUT THERE. 1289 00:49:38,880 --> 00:49:42,200 BUT THIS COVERS THE FIRST 6 TO 7 1290 00:49:42,200 --> 00:49:43,680 WEEKS OF HUMAN CNS DEVELOPMENT, 1291 00:49:43,680 --> 00:49:48,520 STREAMS LINES A -- STREAMLINES 1292 00:49:48,520 --> 00:49:50,160 INTO A SINGLE QUANTITATIVE ASSAY 1293 00:49:50,160 --> 00:49:52,800 THAT LASTS A WEEK WITH A 1294 00:49:52,800 --> 00:49:54,240 SINGULAR READOUT, WORKING ON A 1295 00:49:54,240 --> 00:49:56,880 SECOND GENERATION WHERE THE 1296 00:49:56,880 --> 00:49:57,800 SURFACE WILL INSTRUCT 1297 00:49:57,800 --> 00:49:59,400 MORPHOGENESIS TO COVER A LOT OF 1298 00:49:59,400 --> 00:50:03,600 OTHER ASSAYS AS WELL IN THIS 1299 00:50:03,600 --> 00:50:04,520 SINGLE PLATFORM. 1300 00:50:04,520 --> 00:50:10,200 SO WE KNOW IT WORKS WITH DMSO 1301 00:50:10,200 --> 00:50:17,080 CHEMICAL LIBRARIES, UP TO .1%, 1302 00:50:17,080 --> 00:50:18,320 AND REPRODUCIBILITY WE SCALED 1303 00:50:18,320 --> 00:50:20,200 AND RUN THE ASSAY, SEE THE 1304 00:50:20,200 --> 00:50:22,720 ASSAY, AND GET REALLY GOOD 1305 00:50:22,720 --> 00:50:23,720 EFFICIENCIES ACROSS OUR 1306 00:50:23,720 --> 00:50:25,960 DIFFERENT REGIONS THAT WE'RE 1307 00:50:25,960 --> 00:50:26,240 ASSAYING. 1308 00:50:26,240 --> 00:50:29,520 WE KNOW WE CAN INTEGRATE HUMAN 1309 00:50:29,520 --> 00:50:30,800 METABOLISM INTO THIS ASSAY, NOT 1310 00:50:30,800 --> 00:50:33,200 ONLY TEST CHEMICALS BUT ALSO 1311 00:50:33,200 --> 00:50:34,960 TEST METABOLIZED FORMS, AND 1312 00:50:34,960 --> 00:50:38,680 WE'VE SEEN THAT ACTUALLY CHANGES 1313 00:50:38,680 --> 00:50:40,680 PROFILES, SOME MORE AND SOME 1314 00:50:40,680 --> 00:50:42,640 LESS TOXICS, FOR A SMALL NUMBER 1315 00:50:42,640 --> 00:50:45,520 OF COMPOUNDS, AGAIN FUNDED BY 1316 00:50:45,520 --> 00:50:47,880 NIEHS, TO DO A HUNDRED COMPOUND 1317 00:50:47,880 --> 00:50:49,720 LIBRARIES THAT WE'RE CURRENTLY 1318 00:50:49,720 --> 00:50:52,560 PUSHING AND DOING NOW, BUT WE'VE 1319 00:50:52,560 --> 00:50:54,320 DONE THIS FOR 30 POSITIVE AND 1320 00:50:54,320 --> 00:50:55,880 NEGATIVE CONTROLS FROM 1321 00:50:55,880 --> 00:50:57,760 LITERATURE KNOWN TO CAUSE NEURAL 1322 00:50:57,760 --> 00:50:58,720 TUBE DEFECTS OR DISRUPTION OF 1323 00:50:58,720 --> 00:51:02,960 NEURAL TUBE FORMATION AS WELL AS 1324 00:51:02,960 --> 00:51:12,840 CHEMICALS AND PESTICIDES THAT 1325 00:51:12,840 --> 00:51:14,160 CORRELATE WITH NEURAL TUBE 1326 00:51:14,160 --> 00:51:16,240 DEFECTS SO WE SEE GOOD 1327 00:51:16,240 --> 00:51:16,840 SENSITIVITY AND SPECIFICITY, OF 1328 00:51:16,840 --> 00:51:18,520 COURSE THIS IS A SMALL NUMBER OF 1329 00:51:18,520 --> 00:51:20,480 COMPOUNDS BUT WE'RE RAMPING UP 1330 00:51:20,480 --> 00:51:21,920 AND DOING MORE. 1331 00:51:21,920 --> 00:51:25,320 WE SEE UNIQUE DOSE-RESPONSE IF 1332 00:51:25,320 --> 00:51:28,800 YOU'RE LOOKING AT FORE BRAIN 1333 00:51:28,800 --> 00:51:31,120 VERSUS SPINAL ROSETTE ARRAYSA 1334 00:51:31,120 --> 00:51:33,560 CRITICAL FACTOR BECAUSE RODENT 1335 00:51:33,560 --> 00:51:37,040 MODELS FOR TUBE DEFECTS OCCUR IN 1336 00:51:37,040 --> 00:51:38,600 THE FOREBRAIN, THERE'S ONE OUT 1337 00:51:38,600 --> 00:51:40,760 OF 400 THAT SHOWS A SPINAL 1338 00:51:40,760 --> 00:51:41,040 PHENOTYPE. 1339 00:51:41,040 --> 00:51:44,920 IN HUMANS THE CLINICAL ASSAY, 1340 00:51:44,920 --> 00:51:45,640 CLINICAL PRESENTATION, IS 1341 00:51:45,640 --> 00:51:49,080 PRIMARILY SPINA BIFIDA AND SO WE 1342 00:51:49,080 --> 00:51:51,480 SEE THAT RESPONDING ROSETTE 1343 00:51:51,480 --> 00:51:52,600 RATES ARE SENSITIVE TO MOST 1344 00:51:52,600 --> 00:51:57,720 COMPOUNDS IN THE FOREBRAINS 1345 00:51:57,720 --> 00:51:59,720 RECAPITULATING ASPECTS OF CNS 1346 00:51:59,720 --> 00:52:00,480 DEVELOPMENT. 1347 00:52:00,480 --> 00:52:02,760 WE'RE READY FOR SORT OF DIPPING 1348 00:52:02,760 --> 00:52:05,360 OUR TOES INTO GETTING THIS INTO 1349 00:52:05,360 --> 00:52:07,760 REGULATORY HANDS AND TESTING 1350 00:52:07,760 --> 00:52:10,040 THIS AND WE HAVE GUIDANCE 1351 00:52:10,040 --> 00:52:13,400 DOCUMENTS, STARTING TO DO PLAN 1352 00:52:13,400 --> 00:52:15,400 FOR REGULATORY INTRODUCTION OF 1353 00:52:15,400 --> 00:52:17,560 THE ASSAY, AND SO WE'LL BE 1354 00:52:17,560 --> 00:52:19,640 READING THROUGH THOSE AND 1355 00:52:19,640 --> 00:52:20,280 CONTACTING YOU, WE ALREADY 1356 00:52:20,280 --> 00:52:22,160 REACHED OUT TO A COUPLE. 1357 00:52:22,160 --> 00:52:25,000 OUR GOAL TO ALLOW THE COMMUNITY 1358 00:52:25,000 --> 00:52:26,520 TO CONDUCT DEVELOPMENTAL 1359 00:52:26,520 --> 00:52:29,280 NEUROTOX IS ISTY IN A 1360 00:52:29,280 --> 00:52:32,320 QUANTITATIVE HIGH-THROUGHPUT 1361 00:52:32,320 --> 00:52:33,200 FORMAT, WONDERFUL ASSAY, HIGHLY 1362 00:52:33,200 --> 00:52:34,400 REPRODUCE ABLE FOR THE GOAL. 1363 00:52:34,400 --> 00:52:37,320 WE DO THIS AS A CONTRACT 1364 00:52:37,320 --> 00:52:40,960 RESEARCH SERVICE, WHERE WE CAN 1365 00:52:40,960 --> 00:52:42,280 CONDUCT SCREENS. 1366 00:52:42,280 --> 00:52:48,080 IF YOU'RE INTERESTED IN 1367 00:52:48,080 --> 00:52:50,400 COLLABORATIONS PLEASE CONTACT 1368 00:52:50,400 --> 00:52:50,560 US. 1369 00:52:50,560 --> 00:52:52,440 THE PLATES WE CAN SELL RIGHT 1370 00:52:52,440 --> 00:52:53,240 NOW. 1371 00:52:53,240 --> 00:52:54,880 WE'RE FINISHING LICENSES WITH 1372 00:52:54,880 --> 00:52:55,960 WISCONSIN, WE'LL BE ABLE TO SELL 1373 00:52:55,960 --> 00:52:59,280 A FULL KIT IN THE NEAR FUTURE SO 1374 00:52:59,280 --> 00:53:00,680 PEOPLE CAN CONDUCT ASSAYS AS 1375 00:53:00,680 --> 00:53:02,080 THEIR OWN FACILITY. 1376 00:53:02,080 --> 00:53:05,320 WE HAVE A WEB ACCESSIBLE IMAGE 1377 00:53:05,320 --> 00:53:07,360 SOFTWARE BETA TESTED, THAT WILL 1378 00:53:07,360 --> 00:53:08,240 BE AVAILABLE SOON, SUCH THAT 1379 00:53:08,240 --> 00:53:10,760 WHEN YOU USE A SINGLE PLATE AND 1380 00:53:10,760 --> 00:53:12,640 GENERATE 4,000 IMAGES, YOU CAN 1381 00:53:12,640 --> 00:53:14,360 UPLOAD THOSE TO HAVE THEM 1382 00:53:14,360 --> 00:53:16,360 ANALYZED WITHIN A MATTER OF 1383 00:53:16,360 --> 00:53:16,760 MINUTES. 1384 00:53:16,760 --> 00:53:18,320 WE THINK THIS WILL BE A REALLY 1385 00:53:18,320 --> 00:53:21,240 NICE TOOL FOR THE COMMUNITY TO 1386 00:53:21,240 --> 00:53:22,080 CONDUCT HUMAN DEVELOPMENTAL 1387 00:53:22,080 --> 00:53:23,000 NEUROTOXICITY AND OF COURSE 1388 00:53:23,000 --> 00:53:28,920 WE'RE EXPLORING OTHER AVENUES 1389 00:53:28,920 --> 00:53:29,440 FOR THIS. 1390 00:53:29,440 --> 00:53:31,520 WE HAVE A GRANT FROM NIEHS TO 1391 00:53:31,520 --> 00:53:34,080 TAKE THIS ASSAY THROUGH PACES, 1392 00:53:34,080 --> 00:53:36,240 WE'LL HAVE PUBLICATION COMING 1393 00:53:36,240 --> 00:53:39,000 OUT THIS SUMMER, OR THIS FALL, 1394 00:53:39,000 --> 00:53:40,640 AND THAT WILL INTRODUCE THE 1395 00:53:40,640 --> 00:53:42,040 SCALEUP AND UTILITY OF THIS 1396 00:53:42,040 --> 00:53:46,760 ASSAY AND THEN OF COURSE THAT 1397 00:53:46,760 --> 00:53:47,360 100-POUND SCREEN WE'LL BE 1398 00:53:47,360 --> 00:53:49,800 PUBLISHING THAT IN THE NEAR 1399 00:53:49,800 --> 00:53:51,440 FUTURE AS WELL. 1400 00:53:51,440 --> 00:53:53,520 THIS IS OUR ASSAY. 1401 00:53:53,520 --> 00:53:56,080 OUR MODEL IS HUMAN BRAIN AND 1402 00:53:56,080 --> 00:53:57,480 SPINAL CORD DEVELOPMENT, AND 1403 00:53:57,480 --> 00:54:02,640 THIS TECHNOLOGY WAS ALL FUNDED 1404 00:54:02,640 --> 00:54:05,240 BY REGULATORY FUNDING, BOROUGHS 1405 00:54:05,240 --> 00:54:06,760 WELLCOME, AND THEN EPA, NOW 1406 00:54:06,760 --> 00:54:09,280 NIEHS, SO WE HOPE THAT IT WILL 1407 00:54:09,280 --> 00:54:10,920 BE PUT INTO USE IN THE 1408 00:54:10,920 --> 00:54:11,800 REGULATORY COMMUNITY. 1409 00:54:11,800 --> 00:54:14,200 WITH THAT I'LL TAKE ANY 1410 00:54:14,200 --> 00:54:14,480 QUESTIONS. 1411 00:54:14,480 --> 00:54:17,720 >> THANKS VERY MUCH, RANDY. 1412 00:54:17,720 --> 00:54:19,040 1413 00:54:19,040 --> 00:54:22,480 WE HAVE MAYBE A MINUTE FOR ANY 1414 00:54:22,480 --> 00:54:25,720 QUICK CLARIFYING QUESTION IN THE 1415 00:54:25,720 --> 00:54:26,600 ROOM. 1416 00:54:26,600 --> 00:54:28,000 OKAY, NOT SEEING ANY. 1417 00:54:28,000 --> 00:54:28,800 THANKS VERY MUCH. 1418 00:54:28,800 --> 00:54:33,240 NOW WE'LL GO TO OUR LAST PUBLIC 1419 00:54:33,240 --> 00:54:34,680 COMMENTER, FRANK BARILE FROM 1420 00:54:34,680 --> 00:54:37,280 HUMANE SOCIETY OF THE UNITED 1421 00:54:37,280 --> 00:54:37,520 STATES. 1422 00:54:37,520 --> 00:54:38,080 >> EXCUSE ME, NICOLE? 1423 00:54:38,080 --> 00:54:40,920 >> CHARLES, DO YOU HAVE A 1424 00:54:40,920 --> 00:54:42,040 QUESTION FOR DR. ASHTON? 1425 00:54:42,040 --> 00:54:44,080 >> I DO. 1426 00:54:44,080 --> 00:54:44,280 THANKS. 1427 00:54:44,280 --> 00:54:45,960 I THINK TWO OR THREE SLIDES FROM 1428 00:54:45,960 --> 00:54:52,520 YOUR LAST SLIDE YOU HAD A GRAPH, 1429 00:54:52,520 --> 00:54:55,680 CHARLES KOVATCH, EPA. 1430 00:54:55,680 --> 00:54:59,400 A SLIDE SHOWING THE NEUROROSETTE 1431 00:54:59,400 --> 00:55:00,640 RESPONSE VERSUS I THINK 1432 00:55:00,640 --> 00:55:01,720 CONCENTRATION AND SOMETHING 1433 00:55:01,720 --> 00:55:02,080 ELSE. 1434 00:55:02,080 --> 00:55:03,800 I WONDER IF YOU COULD QUICKLY 1435 00:55:03,800 --> 00:55:06,240 DESCRIBE -- THAT'S THE ONE. 1436 00:55:06,240 --> 00:55:09,080 WHY WERE YOU SEEING -- WHY IS 1437 00:55:09,080 --> 00:55:11,480 THE ROSETTE FORMATION, YOU KNOW, 1438 00:55:11,480 --> 00:55:13,640 SO DIFFERENT THAN THE CELL 1439 00:55:13,640 --> 00:55:15,720 VIABILITY AND NEURAL 1440 00:55:15,720 --> 00:55:16,160 DIFFERENTIAL RATION? 1441 00:55:16,160 --> 00:55:20,240 >> YEAH, THAT'S A GREAT 1442 00:55:20,240 --> 00:55:20,520 QUESTION. 1443 00:55:20,520 --> 00:55:22,840 THE MORPHOGENESIS, THE POWER OF 1444 00:55:22,840 --> 00:55:33,280 ORGANIZE THEY MODEL HUMAN 1445 00:55:35,160 --> 00:55:36,960 MORPHOGENESIS, AND TO OCCUR 1446 00:55:36,960 --> 00:55:37,960 SIMULTANEOUSLY IN AN 1447 00:55:37,960 --> 00:55:42,640 ORCHESTRATED FASHION, WHEN WE 1448 00:55:42,640 --> 00:55:45,280 DID AN ASSAY, BATTERY, THE 1449 00:55:45,280 --> 00:55:47,560 ORCHESTRATION OF THOSE FACETS IS 1450 00:55:47,560 --> 00:55:49,440 WHAT GOVERNS CNS DEVELOPMENT. 1451 00:55:49,440 --> 00:55:53,360 WE OFTEN FIND -- NOT ALWAYS BUT 1452 00:55:53,360 --> 00:55:54,520 WE OFTEN FIND THE FORMATION 1453 00:55:54,520 --> 00:55:56,520 METRIC IS MORE SENSITIVE THAN 1454 00:55:56,520 --> 00:56:00,000 THE OTHER TWO, BECAUSE IF ANY OF 1455 00:56:00,000 --> 00:56:01,880 THE PERTURBATIONS THAT WON'T 1456 00:56:01,880 --> 00:56:05,760 KILL A CELL BUT MAY SLOW DOWN 1457 00:56:05,760 --> 00:56:07,600 PROLIFERATION, THAT ALTERS THE 1458 00:56:07,600 --> 00:56:09,440 ORCHESTRATION OF THAT ENTIRE 1459 00:56:09,440 --> 00:56:12,320 PROCESS TO AFFECT ROSETTE 1460 00:56:12,320 --> 00:56:13,960 FORMATION. 1461 00:56:13,960 --> 00:56:17,240 THE SHORT ANSWER IS LIGHT 1462 00:56:17,240 --> 00:56:18,520 PERTURBATION AND NEURAL 1463 00:56:18,520 --> 00:56:19,760 DIFFERENTIATION OR CELL 1464 00:56:19,760 --> 00:56:21,080 VIABILITY OR PROLIFERATION WOULD 1465 00:56:21,080 --> 00:56:22,360 BE HARD TO DETECT WHEN YOU LOOK 1466 00:56:22,360 --> 00:56:23,720 AT THOSE METRICS. 1467 00:56:23,720 --> 00:56:25,080 WE THINK ARE AMPLIFIED WHEN YOU 1468 00:56:25,080 --> 00:56:31,120 LOOK AT SORT OF THE 1469 00:56:31,120 --> 00:56:32,160 MORPHOGENESIS ASPECT WHICH 1470 00:56:32,160 --> 00:56:33,560 REQUIRES THOSE TO SIMULTANEOUSLY 1471 00:56:33,560 --> 00:56:34,320 OCCUR. 1472 00:56:34,320 --> 00:56:36,320 WE THINK IT'S AMPLIFIED LOOKING 1473 00:56:36,320 --> 00:56:37,800 AT MORPHOGENESIS AND OFTEN FIND 1474 00:56:37,800 --> 00:56:40,800 THAT METRIC IS MORE SENSITIVE. 1475 00:56:40,800 --> 00:56:43,120 >> GREAT. 1476 00:56:43,120 --> 00:56:43,400 THANK YOU. 1477 00:56:43,400 --> 00:56:44,520 >> THANK YOU. 1478 00:56:44,520 --> 00:56:51,760 IT'S REALLY EXCITING TO SEE THE 1479 00:56:51,760 --> 00:56:54,400 PROGRESS THAT'S BEING MADE IN 1480 00:56:54,400 --> 00:56:56,080 THING OR NIGHT SPACE. 1481 00:56:56,080 --> 00:56:59,320 LAST IS FRANK BARILE. 1482 00:56:59,320 --> 00:57:02,880 WE SEE YOUR NAME ONLINE. 1483 00:57:02,880 --> 00:57:04,160 CAN YOU UNMUTE AND -- 1484 00:57:04,160 --> 00:57:08,080 >>CAN YOU HEAR ME? 1485 00:57:08,080 --> 00:57:08,840 >>YES, VERY WELL. 1486 00:57:08,840 --> 00:57:10,200 >> I HAD THE VIDEO ON BUT IT 1487 00:57:10,200 --> 00:57:11,800 DOESN'T SEEM TO BE SHOWING. 1488 00:57:11,800 --> 00:57:22,280 >> UNFORTUNATELY WECANNOT SEE 1489 00:57:29,720 --> 00:57:30,760 YOU. 1490 00:57:30,760 --> 00:57:31,800 >> HOPEFULLY YOU CAN HEAR ME. 1491 00:57:31,800 --> 00:57:32,520 >>WE HEAR YOU WELL. 1492 00:57:32,520 --> 00:57:34,160 >> THANK YOU FOR THE 1493 00:57:34,160 --> 00:57:37,040 OPPORTUNITY TO MAKE THE 1494 00:57:37,040 --> 00:57:38,240 PRESENTATION TODAY, ORAL 1495 00:57:38,240 --> 00:57:39,960 COMMENTS BEING TRANSMITTED TO 1496 00:57:39,960 --> 00:57:44,000 YOU FROM SUNNY TOWN IN SOUTHERN 1497 00:57:44,000 --> 00:57:51,760 ITALY, JUST NORTH OF NAPLES. 1498 00:57:51,760 --> 00:57:53,240 AND SIX HOURS AHEAD, FOUR IN THE 1499 00:57:53,240 --> 00:57:53,680 AFTERNOON. 1500 00:57:53,680 --> 00:57:59,400 ON BEHALF OF THE HUMANE SOCIETY 1501 00:57:59,400 --> 00:58:01,600 OF THE UNITED STATES, HSOF AND 1502 00:58:01,600 --> 00:58:03,080 MEMBERS AND SUPPORTERS, WE 1503 00:58:03,080 --> 00:58:04,960 APPRECIATE THE OPPORTUNITY TO 1504 00:58:04,960 --> 00:58:07,440 PROVIDE COMMENTS IN RESPONSE TO 1505 00:58:07,440 --> 00:58:12,640 THE APRIL 6, 2023 NOTICE, ICCVAM 1506 00:58:12,640 --> 00:58:12,960 PUBLIC FORUM. 1507 00:58:12,960 --> 00:58:16,360 I'D LIKE TO GIVE AN OVERVIEW OF 1508 00:58:16,360 --> 00:58:18,080 THE HISTORICAL ACCOMPLISHMENTS 1509 00:58:18,080 --> 00:58:21,480 ACHIEVED BY ICCVAM SINCE THE 1510 00:58:21,480 --> 00:58:23,560 ESTABLISHMENT AUTHORIZATION ACT 1511 00:58:23,560 --> 00:58:25,320 OF 2000, HR 4281, THE 1512 00:58:25,320 --> 00:58:28,480 ORGANIZATION HAS PROGRESSED IN 1513 00:58:28,480 --> 00:58:29,800 MOVING TOWARD DEVELOPMENT, 1514 00:58:29,800 --> 00:58:31,680 ACCEPTANCE, INCORPORATION OF 1515 00:58:31,680 --> 00:58:32,880 ALTERNATIVE APPROACHES TO ANIMAL 1516 00:58:32,880 --> 00:58:35,160 TESTING IN DRUG AND CHEMICAL 1517 00:58:35,160 --> 00:58:38,080 SAFETY ASSESSMENT. 1518 00:58:38,080 --> 00:58:42,920 THE STRONG LEADERSHIP AT NTP AND 1519 00:58:42,920 --> 00:58:44,120 NICEATM, NON-ANIMAL APPROACHES 1520 00:58:44,120 --> 00:58:45,480 CONTINUE TO BE ACKNOWLEDGED 1521 00:58:45,480 --> 00:58:46,880 THROUGH THE DEVELOPMENT. 1522 00:58:46,880 --> 00:58:50,400 AND ACCEPTANCE IN THE GLOBAL 1523 00:58:50,400 --> 00:58:53,040 TOXICOLOGY TESTING ARENA. 1524 00:58:53,040 --> 00:58:55,120 THROUGH REGULAR ENGAGEMENT WITH 1525 00:58:55,120 --> 00:58:56,320 REGULATORS, INDUSTRY, 1526 00:58:56,320 --> 00:58:58,960 STAKEHOLDERS ON LATEST TESTING 1527 00:58:58,960 --> 00:59:00,840 STRATEGIES, NICEATM PROVIDES 1528 00:59:00,840 --> 00:59:02,120 GUIDELINES, INFORMATION, 1529 00:59:02,120 --> 00:59:03,320 LEADERSHIP ABOUT MODERNIZING 1530 00:59:03,320 --> 00:59:05,840 SAFETY ASSESSMENTS AND 1531 00:59:05,840 --> 00:59:07,080 MINIMIZING ANIMAL USE. 1532 00:59:07,080 --> 00:59:08,920 WHILE WE ARE PLEASED TO SEE THAT 1533 00:59:08,920 --> 00:59:11,760 SOME OF THE ITEMS OF THE ICCVAM 1534 00:59:11,760 --> 00:59:15,800 MEETING FOCUSED ON ADVANCING 1535 00:59:15,800 --> 00:59:17,920 ALTERNATIVES I'M COMPELLED TO 1536 00:59:17,920 --> 00:59:19,120 SHARE HISTORICAL VIEW THAT WHILE 1537 00:59:19,120 --> 00:59:20,960 DEVELOPMENT AND ACCEPTANCE OF 1538 00:59:20,960 --> 00:59:23,240 NEW APPROACH METHODOLOGIES WITH 1539 00:59:23,240 --> 00:59:25,000 REGULATORY AGENCIES AND 1540 00:59:25,000 --> 00:59:25,720 STAKEHOLDERS HAS PROGRESSED, THE 1541 00:59:25,720 --> 00:59:30,160 RATE OF PROGRESS OVER THE LAST 1542 00:59:30,160 --> 00:59:32,640 TWO DECADES IS DISAPPOINTING. 1543 00:59:32,640 --> 00:59:34,080 PARTICULARLY CONCERNING 1544 00:59:34,080 --> 00:59:36,040 REGULATORY ACCEPTANCE OF NAMs. 1545 00:59:36,040 --> 00:59:38,280 SCIENTIFIC DEVELOPMENTS IN THE 1546 00:59:38,280 --> 00:59:41,520 FIELD OF TOXICOLOGY TESTING AND 1547 00:59:41,520 --> 00:59:43,040 PROGRESS ALONGSIDE REGULATORY, 1548 00:59:43,040 --> 00:59:44,480 INDUSTRIAL, PUBLIC STAKEHOLDERS 1549 00:59:44,480 --> 00:59:52,920 HAS BEEN EXPANDING FOR OVER 40 1550 00:59:52,920 --> 00:59:53,440 YEARS. 1551 00:59:53,440 --> 00:59:55,080 INITIAL RECOGNITION HAS BEEN 1552 00:59:55,080 --> 00:59:56,400 HISTORICALLY CHALLENGING. 1553 00:59:56,400 --> 00:59:57,600 SINCE THEN THERE'S BEEN 1554 00:59:57,600 --> 00:59:58,720 ACKNOWLEDGMENT OF SCIENCE AND 1555 00:59:58,720 --> 01:00:00,640 IMPROVEMENT AND ACCEPTANCE OF 1556 01:00:00,640 --> 01:00:02,200 GUIDANCE DOCUMENTS AND 1557 01:00:02,200 --> 01:00:03,880 REGULATORY FRAMEWORKS. 1558 01:00:03,880 --> 01:00:05,680 HOWEVER, THE CURRENT SITUATION 1559 01:00:05,680 --> 01:00:08,080 REGULATORY STATUS OF THE MODELS, 1560 01:00:08,080 --> 01:00:10,440 23 YEARS AFTER THE ESTABLISHMENT 1561 01:00:10,440 --> 01:00:12,960 OF ICCVAM, HAS BEEN SLIGHTLY 1562 01:00:12,960 --> 01:00:15,720 DISAPPOINTING. 1563 01:00:15,720 --> 01:00:19,320 THE NUMBER OF METHODOLOGIES 1564 01:00:19,320 --> 01:00:21,360 ACCEPTED BY OECD AS STANDARD 1565 01:00:21,360 --> 01:00:23,520 BEARER HAS INCREASED, THE NUMBER 1566 01:00:23,520 --> 01:00:25,680 OF PROTOCOLS AND PROCEDURES 1567 01:00:25,680 --> 01:00:30,560 ACCEPTED BY SOME U.S. FEDERAL 1568 01:00:30,560 --> 01:00:33,680 AGENCIES HAVE PROGRESSED SLOWLY. 1569 01:00:33,680 --> 01:00:37,400 A LONG LIST ACCEPTABLE DEMANDS 1570 01:00:37,400 --> 01:00:41,440 ON THE WRITTEN COMMENTS, THERE'S 1571 01:00:41,440 --> 01:00:52,000 A LINK TO THE CITATION, EPA.GOV. 1572 01:01:00,600 --> 01:01:01,960 DESPITE ADVANCEMENTS, TO 1573 01:01:01,960 --> 01:01:03,360 ACCURATELY ASSESS SAFETY AND 1574 01:01:03,360 --> 01:01:08,240 REPLACE ANIMAL TESTING FOR DRUG 1575 01:01:08,240 --> 01:01:10,360 DEVELOPMENT HAS BEEN THE WAY FOR 1576 01:01:10,360 --> 01:01:11,360 TWO DECADES. 1577 01:01:11,360 --> 01:01:13,000 IT'S OUR HOPE ICCVAM WILL 1578 01:01:13,000 --> 01:01:15,520 IMPROVE HISTORICAL RECORD BY 1579 01:01:15,520 --> 01:01:18,160 ASSUMING A MORE ACTIVE ROLE IN 1580 01:01:18,160 --> 01:01:19,120 ENCOURAGING FORMAL ACCEPTANCE OF 1581 01:01:19,120 --> 01:01:23,000 NAMs BY THE MEMBER AGENCIES. 1582 01:01:23,000 --> 01:01:24,920 I'D LIKE TO POINT OUT A FEW 1583 01:01:24,920 --> 01:01:27,000 THINGS ABOUT THE CURRENT LEVEL 1584 01:01:27,000 --> 01:01:30,320 OF TECHNOLOGY MPS AND MAKING 1585 01:01:30,320 --> 01:01:34,000 THEM OVER WITH SYSTEMS AND 1586 01:01:34,000 --> 01:01:36,280 LINKING WITH NAMs, PARTNERSHIP 1587 01:01:36,280 --> 01:01:39,720 BETWEEN NATIONAL CENTER FOR 1588 01:01:39,720 --> 01:01:40,400 ADVANCING TRANSLATIONAL 1589 01:01:40,400 --> 01:01:44,840 SCIENCES, NCATS, DARPA, AND THE 1590 01:01:44,840 --> 01:01:48,120 FDA, THAT INITIATED THE HUMAN 1591 01:01:48,120 --> 01:01:48,800 MICROPHYSIOLOGICAL SYSTEMS, 1592 01:01:48,800 --> 01:01:52,440 ORGANS ON CHIPS FOR DRUG SAFETY 1593 01:01:52,440 --> 01:01:53,840 AND EFFICACY TESTING PROGRAM, 1594 01:01:53,840 --> 01:01:54,680 HAS MET AND SURFACED 1595 01:01:54,680 --> 01:01:57,680 EXPECTATIONS IN THE RAPID 1596 01:01:57,680 --> 01:01:58,280 DEVELOPMENT AND 1597 01:01:58,280 --> 01:01:58,880 COMMERCIALIZATION OF SEVERAL 1598 01:01:58,880 --> 01:02:03,680 ORGAN ON A CHIP SYSTEMS THAT ARE 1599 01:02:03,680 --> 01:02:07,480 IN DIFFERENT PHASES OF 1600 01:02:07,480 --> 01:02:08,080 IMPLEMENTATION AND 1601 01:02:08,080 --> 01:02:08,560 COMMERCIALIZATION, THIS 1602 01:02:08,560 --> 01:02:10,560 COLLABORATION SHOULD SERVE AS 1603 01:02:10,560 --> 01:02:12,080 MODEL FOR OTHER TECHNOLOGY 1604 01:02:12,080 --> 01:02:14,280 DEVELOPMENT PROJECTS, AND FOR 1605 01:02:14,280 --> 01:02:20,280 PROJECTS THAT ADDRESS COMMON 1606 01:02:20,280 --> 01:02:25,880 INFORMATION NEEDS. 1607 01:02:25,880 --> 01:02:27,880 ATTEMPTS AT SIMULATING HAS 1608 01:02:27,880 --> 01:02:29,280 ACHIEVED TREMENDOUS SUCCESS IN 1609 01:02:29,280 --> 01:02:31,400 THE LAST TEN YEARS BUT 1610 01:02:31,400 --> 01:02:35,280 IMPLEMENTATION IS STILL TO BE 1611 01:02:35,280 --> 01:02:37,280 REALIZED. 1612 01:02:37,280 --> 01:02:39,360 AT THE CURRENT RATE 1613 01:02:39,360 --> 01:02:41,000 IMPLEMENTATION WILL PROBABLY NOT 1614 01:02:41,000 --> 01:02:43,800 OCCUR FOR AT LEAST ANOTHER 25 1615 01:02:43,800 --> 01:02:44,080 YEARS. 1616 01:02:44,080 --> 01:02:45,960 THERE'S A TREMENDOUS OPPORTUNITY 1617 01:02:45,960 --> 01:02:54,120 HERE FOR ICCVAM TO ACCELERATE 1618 01:02:54,120 --> 01:02:55,400 THIS TIMELINE. 1619 01:02:55,400 --> 01:02:59,920 COMMENTING ON VALIDATION, WITH 1620 01:02:59,920 --> 01:03:02,360 THE RECOGNITION THAT MANY IN 1621 01:03:02,360 --> 01:03:03,320 VITRO METHODS WERE ENDORSED 10 1622 01:03:03,320 --> 01:03:05,080 TO 15 YEARS AGO NOT INTEGRATED 1623 01:03:05,080 --> 01:03:07,360 OR ACCEPTED BY REGULATORY 1624 01:03:07,360 --> 01:03:11,320 AGENCIES AS APPROVED MODELS FOR 1625 01:03:11,320 --> 01:03:12,200 TOXICITY TESTING ICCVAM 1626 01:03:12,200 --> 01:03:13,760 PUBLISHED A STRATEGIC ROADMAP, 1627 01:03:13,760 --> 01:03:16,000 ALSO THE CITATION IS IN THE 1628 01:03:16,000 --> 01:03:19,760 WRITTEN COMMENTS AS A LINK, 1629 01:03:19,760 --> 01:03:21,360 PUBLISHED STRATEGIC ROADMAP IN 1630 01:03:21,360 --> 01:03:23,600 JANUARY 2018 AS A NEW STRATEGY 1631 01:03:23,600 --> 01:03:25,240 FOR TOXICITY TESTING. 1632 01:03:25,240 --> 01:03:26,880 IN ORDER TO EXPEDITE DEVELOPMENT 1633 01:03:26,880 --> 01:03:29,520 AND USE OF NAMs AND PROVIDE 1634 01:03:29,520 --> 01:03:31,760 INFORMATION MORE RELEVANT TO 1635 01:03:31,760 --> 01:03:34,320 HUMAN HEALTH AND EXISTING 1636 01:03:34,320 --> 01:03:35,720 ANIMAL-BASED METHODS. 1637 01:03:35,720 --> 01:03:36,280 SUCCESSFUL DEVELOPMENT AND 1638 01:03:36,280 --> 01:03:38,360 IMPLEMENTATION OF THESE NOVEL 1639 01:03:38,360 --> 01:03:40,440 AND INNOVATIVE APPROACHES 1640 01:03:40,440 --> 01:03:41,880 REQUIRES COORDINATED EFFORTS, 1641 01:03:41,880 --> 01:03:44,520 THAT ADDRESS THREE STRATEGIC 1642 01:03:44,520 --> 01:03:44,720 GOALS. 1643 01:03:44,720 --> 01:03:50,960 CONNECT END USERS WITH 1644 01:03:50,960 --> 01:03:52,000 DEVELOPERS 1645 01:03:52,000 --> 01:03:54,000 USE OF ROBUST PRACTICES, AND, 1646 01:03:54,000 --> 01:03:54,680 THREE, ENCOURAGE ADOPTION AND 1647 01:03:54,680 --> 01:03:56,840 ALLS OF NEW METHODS AND 1648 01:03:56,840 --> 01:04:01,360 APPROACHES BY FEDERAL AGENCIES 1649 01:04:01,360 --> 01:04:06,920 AND REGULATED INDUSTRIES. 1650 01:04:06,920 --> 01:04:08,360 RECENTLY, PUBLICATION OF 2022 1651 01:04:08,360 --> 01:04:12,840 AGAIN CITATION HAS A LINK IN THE 1652 01:04:12,840 --> 01:04:15,800 WRITTEN COMMENTS, IN THE 1653 01:04:15,800 --> 01:04:18,640 PUBLICATION ENTITLED A FRAMEWORK 1654 01:04:18,640 --> 01:04:19,960 FOR ESTABLISHING SCIENTIFIC 1655 01:04:19,960 --> 01:04:22,080 CONFIDENCE IN NEW APPROACH 1656 01:04:22,080 --> 01:04:24,240 METHODOLOGIES OFFER A MODERN 1657 01:04:24,240 --> 01:04:26,440 FLEXIBLE BASIS TO ESTABLISH 1658 01:04:26,440 --> 01:04:28,200 SCIENTIFIC CONFIDENCE IN NAMs 1659 01:04:28,200 --> 01:04:29,600 THAT REGULATORY ASSESSMENT OF 1660 01:04:29,600 --> 01:04:32,120 CHEMICALS FOR HUMAN HEALTH 1661 01:04:32,120 --> 01:04:33,760 EFFECTS, THE AUTHORS PROPOSE, I 1662 01:04:33,760 --> 01:04:34,960 QUOTE, FIVE ESSENTIAL ELEMENTS 1663 01:04:34,960 --> 01:04:36,920 THAT FORM THE BASIS OF A 1664 01:04:36,920 --> 01:04:38,800 FRAMEWORK THAT CAN BE APPLIED BY 1665 01:04:38,800 --> 01:04:43,480 REGULATORS OR OTHER END USERS TO 1666 01:04:43,480 --> 01:04:45,040 ESTABLISH CONFIDENCE IN NAMs 1667 01:04:45,040 --> 01:04:46,800 USED INTERNATIONALLY TO ASSESS 1668 01:04:46,800 --> 01:04:48,440 POTENTIAL CHEMICAL EFFECTS ON 1669 01:04:48,440 --> 01:04:51,040 HUMANS AND PROVIDE INFORMATION 1670 01:04:51,040 --> 01:04:53,960 NEEDED FOR REGULATORY DECISION 1671 01:04:53,960 --> 01:04:57,000 MAKING, END QUOTE. 1672 01:04:57,000 --> 01:04:59,000 INTENDED TO PROVIDE CLARITY, IN 1673 01:04:59,000 --> 01:05:00,840 MODELS, AND ESTABLISH A PROCESS 1674 01:05:00,840 --> 01:05:03,680 FOR DETERMINING THE ADEQUACY OF 1675 01:05:03,680 --> 01:05:04,680 NAMs, OVERALL PERFORMANCE. 1676 01:05:04,680 --> 01:05:07,440 TOGETHER AS PART OF INTEGRATED 1677 01:05:07,440 --> 01:05:09,480 APPROACH TESTING AND ASSESSMENT, 1678 01:05:09,480 --> 01:05:11,920 OR AS STAND ALONE ASSAYS. 1679 01:05:11,920 --> 01:05:14,360 THE FRAMEWORK CONSISTS OF FIVE 1680 01:05:14,360 --> 01:05:17,280 ESSENTIAL ELEMENTS, WHICH HAVE 1681 01:05:17,280 --> 01:05:20,920 BEEN NOTED IN PREVIOUS 1682 01:05:20,920 --> 01:05:22,240 PRESENTATIONS YESTERDAY. 1683 01:05:22,240 --> 01:05:24,200 THEY INCLUDE FITNESS FOR 1684 01:05:24,200 --> 01:05:27,920 PURPOSE, HUMAN BIOLOGICAL 1685 01:05:27,920 --> 01:05:28,520 RELEVANCE, TECHNICAL 1686 01:05:28,520 --> 01:05:32,080 CHARACTERIZATION, DATA INTEGRITY 1687 01:05:32,080 --> 01:05:34,040 AND TRANSPARENCY, INDEPENDENT 1688 01:05:34,040 --> 01:05:35,360 REVIEW. 1689 01:05:35,360 --> 01:05:37,880 THIS FRAMEWORK AND ELEMENTS 1690 01:05:37,880 --> 01:05:41,040 BEARS RESEMBLANCE TO VARIOUS 1691 01:05:41,040 --> 01:05:42,040 OTHER HISTORICAL PROPOSALS MADE 1692 01:05:42,040 --> 01:05:46,680 BY A NUMBER OF AUTHORS AND 1693 01:05:46,680 --> 01:05:48,480 ORIGINALLY DESCRIBED EARLIER IN 1694 01:05:48,480 --> 01:05:48,840 1994. 1695 01:05:48,840 --> 01:05:54,200 AND LATER CHARACTERIZED IN 1696 01:05:54,200 --> 01:05:55,520 GUIDANCE DOCUMENTs BY OECD 1697 01:05:55,520 --> 01:05:57,920 BOTH WITH CITATIONS IN WRITTEN 1698 01:05:57,920 --> 01:05:58,160 COMMENTS. 1699 01:05:58,160 --> 01:05:59,360 SOME CORRESPONDING COMPARABLE 1700 01:05:59,360 --> 01:06:02,160 TERMS AND PROPOSED DEFINITIONS 1701 01:06:02,160 --> 01:06:05,680 SUCH AS RELEVANCE, RELIABILITY, 1702 01:06:05,680 --> 01:06:08,400 SENSITIVITY, SPECIFICITY, 1703 01:06:08,400 --> 01:06:09,520 STANDARDIZATION, AND 1704 01:06:09,520 --> 01:06:10,800 MULTI-LABORATORY MULTI-METHOD 1705 01:06:10,800 --> 01:06:13,600 PROGRAMS, MANY WERE PROMOTED AS 1706 01:06:13,600 --> 01:06:17,640 PART OF VALIDATION PROGRAMS FOR 1707 01:06:17,640 --> 01:06:19,400 ACUTE ORAL, DERMAL, TOXICITY 1708 01:06:19,400 --> 01:06:22,240 TESTING TOOK YEARS TO COMPLETE 1709 01:06:22,240 --> 01:06:23,680 AND THEN WEREN'T FULLY 1710 01:06:23,680 --> 01:06:25,320 INTEGRATED BY ALL AGENCIES. 1711 01:06:25,320 --> 01:06:26,920 THE POINT OF THIS BEING THE 1712 01:06:26,920 --> 01:06:29,320 ICCVAM CAN PROVIDE GUIDANCE AND 1713 01:06:29,320 --> 01:06:30,240 ENCOURAGE AGENCIES TO 1714 01:06:30,240 --> 01:06:32,600 ACKNOWLEDGE AND ACCEPT NEW 1715 01:06:32,600 --> 01:06:33,200 FRAMEWORK WHILE INCORPORATING 1716 01:06:33,200 --> 01:06:37,200 SOME OF THE OLD FRAMEWORKS SO 1717 01:06:37,200 --> 01:06:38,320 THAT REPETITION AND 1718 01:06:38,320 --> 01:06:39,600 CLARIFICATION SAME OR SIMILAR 1719 01:06:39,600 --> 01:06:42,200 TERMS IN THE NEXT 20 YEARS DOES 1720 01:06:42,200 --> 01:06:43,880 NOT IMPEDE PROGRESS WITH 1721 01:06:43,880 --> 01:06:48,400 STANDARDIZATION AND VALIDATION 1722 01:06:48,400 --> 01:06:50,680 OF NEW METHODOLOGIES. 1723 01:06:50,680 --> 01:06:53,200 AND ICCVAM GROUP WAS ESTABLISHED 1724 01:06:53,200 --> 01:06:55,600 IN 2021 CREATE NEW VALIDATION 1725 01:06:55,600 --> 01:06:57,240 SCHEME WHICH WE ANTICIPATE WILL 1726 01:06:57,240 --> 01:07:02,040 SOON RELEASE A DRAFT UPDATING 1727 01:07:02,040 --> 01:07:03,920 1997 DOCUMENT. 1728 01:07:03,920 --> 01:07:05,320 CITATION LINK. 1729 01:07:05,320 --> 01:07:06,880 WE REQUEST THAT ICCVAM TO 1730 01:07:06,880 --> 01:07:10,560 ENCOURAGE ITS MEMBER AGENCIES TO 1731 01:07:10,560 --> 01:07:11,440 EMBRACE THIS APPROACH, CREATING 1732 01:07:11,440 --> 01:07:13,200 SCIENTIFIC CONFIDENCE NEEDED TO 1733 01:07:13,200 --> 01:07:15,720 ADVANCE NAMs IN A TANGIBLE 1734 01:07:15,720 --> 01:07:17,400 WAY. 1735 01:07:17,400 --> 01:07:19,240 IN CONCLUSION, TO SUCCESSFULLY 1736 01:07:19,240 --> 01:07:20,080 IMPLEMENT ORIGINAL OBJECTIVES 1737 01:07:20,080 --> 01:07:22,640 ESTABLISHED WITH THE FORMATION 1738 01:07:22,640 --> 01:07:24,160 OF ICCVAM, FURTHER REDUCE 1739 01:07:24,160 --> 01:07:28,520 RELIANCE ON ANIMAL TEST METHODS, 1740 01:07:28,520 --> 01:07:29,960 HSUS AND HSLF URGE MEMBER 1741 01:07:29,960 --> 01:07:31,840 AGENCIES TO FOCUS ON 1742 01:07:31,840 --> 01:07:33,720 COORDINATING EFFORTS TO ENSURE 1743 01:07:33,720 --> 01:07:36,400 NAMs ARE ACCEPTED FOR LAYINGER 1744 01:07:36,400 --> 01:07:39,720 TO USE, ALSO PROTECTING HUMAN 1745 01:07:39,720 --> 01:07:43,960 AND ENVIRONMENTAL SAFETY. 1746 01:07:43,960 --> 01:07:45,840 HSLF AND HSUS WILL WORK WITH 1747 01:07:45,840 --> 01:07:47,400 NICEATM OR ANY ICCVAM AGENCY TO 1748 01:07:47,400 --> 01:07:52,920 HAVE ACHIEVED COMMON GOAL OF 1749 01:07:52,920 --> 01:07:54,440 REPLACING ANIMALS WITH RELEVANT 1750 01:07:54,440 --> 01:07:54,760 STRATEGIES. 1751 01:07:54,760 --> 01:07:59,000 THANKS FOR YOUR CONSIDERATION OF 1752 01:07:59,000 --> 01:07:59,360 THESE COMMENTS. 1753 01:07:59,360 --> 01:08:02,000 >> THANK YOU VERY MUCH. 1754 01:08:02,000 --> 01:08:05,520 THAT WAS AN EXCELLENT SEGUE INTO 1755 01:08:05,520 --> 01:08:06,960 THE PRESENTATIONS THAT MYSELF 1756 01:08:06,960 --> 01:08:09,360 AND DR. DAVE ALLEN WILL GIVE 1757 01:08:09,360 --> 01:08:10,800 LATER IN THE AGENDA BECAUSE 1758 01:08:10,800 --> 01:08:13,400 THERE WERE A NUMBER OF TOPICS 1759 01:08:13,400 --> 01:08:15,360 MENTIONED IN THOSE COMMENTS WE 1760 01:08:15,360 --> 01:08:16,480 WILL PROVIDE SOME FEEDBACK AND 1761 01:08:16,480 --> 01:08:19,560 UPDATES ON. 1762 01:08:19,560 --> 01:08:20,120 APPRECIATE THAT. 1763 01:08:20,120 --> 01:08:22,920 WE'RE OUT OF TIME FOR THIS 1764 01:08:22,920 --> 01:08:26,120 PARTICULAR AGENDA ITEM. 1765 01:08:26,120 --> 01:08:28,840 WE NOW ARE ABLE TO REVISIT 1766 01:08:28,840 --> 01:08:30,840 PRESENTATION THAT WAS SCHEDULED 1767 01:08:30,840 --> 01:08:39,720 FOR YESTERDAY BUT WERE ABLE TO 1768 01:08:39,720 --> 01:08:41,480 REARRANGE THE AGENDA AND DR. 1769 01:08:41,480 --> 01:08:43,080 LATHROP IS ONLINE TO GIVE A 1770 01:08:43,080 --> 01:08:44,000 DEVELOPMENT ON THEIR PROGRESS ON 1771 01:08:44,000 --> 01:08:45,360 NINE, V.A. OFFICE OF RESEARCH 1772 01:08:45,360 --> 01:08:47,600 AND DEVELOPMENT. 1773 01:08:47,600 --> 01:08:50,120 >> LET ME SEND MY APOLOGIES FOR 1774 01:08:50,120 --> 01:08:52,120 NOT BEING ABLE TO BE ALONG 1775 01:08:52,120 --> 01:08:54,440 YESTERDAY. 1776 01:08:54,440 --> 01:08:57,160 I HAD A COUPLE PROBLEMS. 1777 01:08:57,160 --> 01:09:00,200 I GOT TO PARTICIPATE IN JUDGING 1778 01:09:00,200 --> 01:09:04,120 POSTERS FOR POSTDOCS AND 1779 01:09:04,120 --> 01:09:07,840 RESEARCHERS AT ATLANTA V.A. 1780 01:09:07,840 --> 01:09:10,080 ANNUAL NOW SECOND ANNUAL 1781 01:09:10,080 --> 01:09:11,320 RESEARCH DAY. 1782 01:09:11,320 --> 01:09:15,240 BUT, AGAIN, THANKFUL TO BE HERE. 1783 01:09:15,240 --> 01:09:18,560 I'M THE CHIEF VETERINARY MEDICAL 1784 01:09:18,560 --> 01:09:25,240 CENTER FOR VETERANS 1785 01:09:25,240 --> 01:09:27,520 ADMINISTRATION, AND NEXT SLIDE. 1786 01:09:27,520 --> 01:09:27,920 ADVANCE. 1787 01:09:27,920 --> 01:09:31,120 >> I'M GETTING THERE. 1788 01:09:31,120 --> 01:09:32,480 THERE WE GO. 1789 01:09:32,480 --> 01:09:37,800 >> THE V.A., WE'RE THE NEWEST 1790 01:09:37,800 --> 01:09:39,440 MEMBER OF ICCVAM, JOINED A 1791 01:09:39,440 --> 01:09:41,760 COUPLE YEARS AGO. 1792 01:09:41,760 --> 01:09:43,360 THE PREMISE FOR US JOINING WAS 1793 01:09:43,360 --> 01:09:46,920 THE FACT V.A. WAS REQUIRED BY 1794 01:09:46,920 --> 01:09:47,840 LAW FIVE-YEAR PLAN NOW, WE'RE IN 1795 01:09:47,840 --> 01:09:53,360 THE THIRD YEAR OF THAT, TO 1796 01:09:53,360 --> 01:09:55,440 ELIMINATE EITHER REDUCE, REFINE, 1797 01:09:55,440 --> 01:09:59,920 OR ELIMINATE USE OF CANINES, 1798 01:09:59,920 --> 01:10:01,560 FELINES, NON-HUMAN PRIMATES IN 1799 01:10:01,560 --> 01:10:03,520 OUR RESEARCH ENVIRONMENT. 1800 01:10:03,520 --> 01:10:05,600 WE'VE BEEN VERY SUCCESSFUL ON 1801 01:10:05,600 --> 01:10:06,360 THAT. 1802 01:10:06,360 --> 01:10:09,960 AS YOU CAN SEE, PUBLIC LAW 1803 01:10:09,960 --> 01:10:16,800 116-94, THIS IS ONE OF MY FIRST 1804 01:10:16,800 --> 01:10:18,560 FORAYS INTO BEING MANDATED TO 1805 01:10:18,560 --> 01:10:20,400 REDUCE USE OF ANIMALS AND IT HAS 1806 01:10:20,400 --> 01:10:21,280 WORKED OUT. 1807 01:10:21,280 --> 01:10:22,920 NEXT SLIDE. 1808 01:10:22,920 --> 01:10:28,480 AS YOU CAN SEE, STARTED IN 2018 1809 01:10:28,480 --> 01:10:34,080 WITH 2019 AND 2020, FINAL 1810 01:10:34,080 --> 01:10:36,720 ITERATION IS A WELL-DESIGNED 1811 01:10:36,720 --> 01:10:37,680 (INDISCERNIBLE) AND WE'RE 1812 01:10:37,680 --> 01:10:38,480 HEARING FROM THAT. 1813 01:10:38,480 --> 01:10:41,400 ONE OF THE PARTS WE SUDDENLY 1814 01:10:41,400 --> 01:10:43,920 REALIZED IN. 1815 01:10:43,920 --> 01:10:47,320 V.A. I'VE BEEN IN THIS 2 1/2 1816 01:10:47,320 --> 01:10:50,600 YEARS, ROOM FOR US TO IMPROVE 1817 01:10:50,600 --> 01:10:53,680 USING ANIMALS FOR RESEARCH TO 1818 01:10:53,680 --> 01:10:54,840 INVOLVE NAMs IN RESEARCH 1819 01:10:54,840 --> 01:10:56,840 APPROACHES TOO. 1820 01:10:56,840 --> 01:10:59,160 WE WENT TO ICCVAM, AND I LEARNED 1821 01:10:59,160 --> 01:11:02,520 QUITE A BIT IN 2 1/2 YEARS, 1822 01:11:02,520 --> 01:11:04,520 PRETTY MUCH MORE PURE ANIMAL 1823 01:11:04,520 --> 01:11:07,680 USERS MOST OF MY CAREER INTO 1824 01:11:07,680 --> 01:11:11,400 USING USE OF NAMs AND 1825 01:11:11,400 --> 01:11:12,520 EDUCATING RESEARCH OTHERS 1826 01:11:12,520 --> 01:11:18,400 DIFFERENT AVENUES, DIFFERENT 1827 01:11:18,400 --> 01:11:18,720 APPROACHES. 1828 01:11:18,720 --> 01:11:20,280 NEXT. 1829 01:11:20,280 --> 01:11:23,640 SO, FIRST THING I DO, WENT OUT 1830 01:11:23,640 --> 01:11:25,840 AND IDENTIFIED WHAT ARE SOME 1831 01:11:25,840 --> 01:11:31,000 RESEARCHERS ACROSS THE UNITED 1832 01:11:31,000 --> 01:11:33,440 STATES DOING, WE HAVE 70 1833 01:11:33,440 --> 01:11:37,680 RESEARCH MODALITIES IN OUR 1834 01:11:37,680 --> 01:11:46,120 VETERANS HOSPITALS ACROSS THE 1835 01:11:46,120 --> 01:11:47,960 UNITED STATES, MICRO FLUEDIC 1836 01:11:47,960 --> 01:11:49,280 TUBULAR, FUNCTIONAL TISSUE 1837 01:11:49,280 --> 01:11:53,440 MODEL, IN VITRO MODELS OF 1838 01:11:53,440 --> 01:11:53,800 TOXOPLASMOSIS. 1839 01:11:53,800 --> 01:11:58,800 ONE OF THE FIRST THINGS WE DID, 1840 01:11:58,800 --> 01:12:00,320 EXECUTIVE COMMITTEE FORMED, MUCH 1841 01:12:00,320 --> 01:12:04,320 TO THE V.A.'S CREDIT WE HAVE NOW 1842 01:12:04,320 --> 01:12:07,080 PUT OUT RFAs FOR DEVELOPING 1843 01:12:07,080 --> 01:12:09,480 AND VALIDATING ALTERNATIVES FOR 1844 01:12:09,480 --> 01:12:12,120 CANINES, FELINES, NON-HUMAN 1845 01:12:12,120 --> 01:12:13,960 PRIMATE, AND THANKS TO OUR 1846 01:12:13,960 --> 01:12:15,400 ADMINISTRATION WE'VE EXTENDED 1847 01:12:15,400 --> 01:12:17,440 THAT TO DEVELOPING AND 1848 01:12:17,440 --> 01:12:20,200 VALIDATING ALTERNATIVES TO USE 1849 01:12:20,200 --> 01:12:23,560 OF ANIMALS IN RESEARCH ACROSS 1850 01:12:23,560 --> 01:12:27,960 OUR RESEARCH ENDEAVORS. 1851 01:12:27,960 --> 01:12:28,280 NEXT. 1852 01:12:28,280 --> 01:12:33,440 AND SO PROGRAMMATIC APPROACH TO 1853 01:12:33,440 --> 01:12:35,480 ALTERNATIVE METHODS HOW WE'VE 1854 01:12:35,480 --> 01:12:37,240 BEEN UTILIZING OUR MONEY, 1855 01:12:37,240 --> 01:12:38,800 UTILIZING OUR EFFORTS, ONE THING 1856 01:12:38,800 --> 01:12:42,280 WE DO IS EXPAND OPPORTUNITIES TO 1857 01:12:42,280 --> 01:12:45,120 UTILIZE ALTERNATIVE METHODS TO 1858 01:12:45,120 --> 01:12:46,720 MEMORANDUMS ARE OUR AFFILIATES. 1859 01:12:46,720 --> 01:12:48,200 V.A. STRUCTURE IS THAT. 1860 01:12:48,200 --> 01:12:50,720 WE USE A LOT OF UNIVERSITIES AND 1861 01:12:50,720 --> 01:12:53,360 OTHER AFFILIATES TO GET OUR 1862 01:12:53,360 --> 01:12:54,120 RESEARCH ACCOMPLISHED. 1863 01:12:54,120 --> 01:12:59,480 AND ALL OF OUR MOUs IN THE 1864 01:12:59,480 --> 01:13:01,360 LAST TWO YEARS, WE'RE UTILIZING 1865 01:13:01,360 --> 01:13:03,640 THESE AFFILIATES AND THEIR 1866 01:13:03,640 --> 01:13:06,240 APPROACH TO NAMs AND MAKING IT 1867 01:13:06,240 --> 01:13:10,960 A UNIFIED APPROACH WITH V.A. 1868 01:13:10,960 --> 01:13:11,960 WE'VE SIGNIFICANTLY EXPANDED 1869 01:13:11,960 --> 01:13:15,120 MONETARY INCENTIVES. 1870 01:13:15,120 --> 01:13:16,760 NOW INVESTIGATORS CAN ACTUALLY, 1871 01:13:16,760 --> 01:13:20,160 IF THEY HAVE ARE DEVELOPING 1872 01:13:20,160 --> 01:13:23,760 ALTERNATIVE METHOD, THEY CAN 1873 01:13:23,760 --> 01:13:24,880 APPLY TO ANIMAL MODELS AND WE 1874 01:13:24,880 --> 01:13:26,160 WILL FUND THEM. 1875 01:13:26,160 --> 01:13:29,680 TO DATE WE HAVE THREE FUNDED 1876 01:13:29,680 --> 01:13:32,080 STUDIES, AND WE'RE ANTICIPATING 1877 01:13:32,080 --> 01:13:33,520 MANY MORE. 1878 01:13:33,520 --> 01:13:35,480 WE'VE DEVELOPED REVIEW CRITERIA, 1879 01:13:35,480 --> 01:13:37,240 ONE THING MISSING IN V.A. 1880 01:13:37,240 --> 01:13:39,560 APPROACH TO USING NAMs WAS 1881 01:13:39,560 --> 01:13:41,040 INVESTIGATORS WERE NOT QUITE 1882 01:13:41,040 --> 01:13:42,160 AWARE OF IT. 1883 01:13:42,160 --> 01:13:44,040 THANKS TO OUR EXECUTIVE 1884 01:13:44,040 --> 01:13:50,040 COMMITTEE, WE NOW HAVE A VERY 1885 01:13:50,040 --> 01:13:50,680 REASONABLE SUPPLEMENTAL 1886 01:13:50,680 --> 01:13:51,920 EDUCATION PROGRAMS, WE REACH OUT 1887 01:13:51,920 --> 01:13:53,200 TO INVESTIGATORS, MAKE SURE THEY 1888 01:13:53,200 --> 01:13:58,920 ARE AWARE OF ALL THE TOOLS 1889 01:13:58,920 --> 01:13:59,880 ICCVAM OFFERS AND ALTERNATIVE 1890 01:13:59,880 --> 01:14:01,400 METHODS WE OFFER AND ARE 1891 01:14:01,400 --> 01:14:02,160 AVAILABLE. 1892 01:14:02,160 --> 01:14:03,800 ONE OF THE OUTCOMES WILL BE FOR 1893 01:14:03,800 --> 01:14:11,040 THE V.A., COME BOOK IS THIS 1894 01:14:11,040 --> 01:14:14,320 APPROACH LATE, I SEE HOW WE 1895 01:14:14,320 --> 01:14:16,400 TRANSITIONED ANIMAL STUDIES 1896 01:14:16,400 --> 01:14:17,160 TOWARDS NAMs. 1897 01:14:17,160 --> 01:14:20,280 SEEING WHICH ONE CAN BE 1898 01:14:20,280 --> 01:14:27,880 REPLACED, WHERE WE HAD SUCCESS, 1899 01:14:27,880 --> 01:14:30,400 ALSO GENERATING ALTERNATIVE 1900 01:14:30,400 --> 01:14:31,040 APPROACHES. 1901 01:14:31,040 --> 01:14:32,920 TO MONITOR THIS PROGRESS HAVE 1902 01:14:32,920 --> 01:14:34,880 RETAINED SERVICES OF INDEPENDENT 1903 01:14:34,880 --> 01:14:36,360 RESEARCH ORGANIZATION, ANALYZE 1904 01:14:36,360 --> 01:14:39,120 AND EVALUATE NOT ONLY 1905 01:14:39,120 --> 01:14:39,920 REFINEMENT, REDUCTION, 1906 01:14:39,920 --> 01:14:40,920 ELIMINATION, THEY ARE 1907 01:14:40,920 --> 01:14:43,400 INCORPORATING ANALYSIS HOW WE'RE 1908 01:14:43,400 --> 01:14:44,280 ACTIVELY PROMOTING ALTERNATIVE 1909 01:14:44,280 --> 01:14:46,240 METHODS AND HOW EFFICIENT AND 1910 01:14:46,240 --> 01:14:51,720 HOW SUCCESSFUL THE V.A. HAS BEEN 1911 01:14:51,720 --> 01:14:53,880 IN ALTERING OUR APPROACH, WHY 1912 01:14:53,880 --> 01:14:55,880 NOT ANIMAL RESEARCH FOR SOME 1913 01:14:55,880 --> 01:14:56,080 AREAS. 1914 01:14:56,080 --> 01:15:04,520 ONE OF THE THINGS EVERYBODY IS 1915 01:15:04,520 --> 01:15:06,480 AWARE OF, IN CONGRESS, A LOT OF 1916 01:15:06,480 --> 01:15:09,000 V.A.s DO USE ANIMALS IN 1917 01:15:09,000 --> 01:15:11,760 RESEARCH AREAS OUT THERE, MOST 1918 01:15:11,760 --> 01:15:13,480 APPROACHES TO THE PATH ACT 1919 01:15:13,480 --> 01:15:18,200 BECAUSE OF BURN PIT EXPOSURE AND 1920 01:15:18,200 --> 01:15:19,440 OTHER EXPOSURES, TOXICOLOGICAL 1921 01:15:19,440 --> 01:15:23,360 EXPOSURES THEY INCORPORATED IS 1922 01:15:23,360 --> 01:15:27,160 PUSHING TO NON-TRADITIONAL, YOU 1923 01:15:27,160 --> 01:15:30,480 KNOW, ALTERNATIVE METHODS. 1924 01:15:30,480 --> 01:15:30,680 NEXT. 1925 01:15:30,680 --> 01:15:32,440 FOR THOSE WHO WANT TO FIND OUT 1926 01:15:32,440 --> 01:15:35,080 HOW WELL WE'RE DOING, V.A. IS 1927 01:15:35,080 --> 01:15:36,160 VERY, VERY TRANSPARENT. 1928 01:15:36,160 --> 01:15:41,200 YOU CAN GO TO OUR V.A. ANIMAL 1929 01:15:41,200 --> 01:15:43,840 RESEARCH PROGRAM TO FIND OUT HOW 1930 01:15:43,840 --> 01:15:44,560 WE'RE ALTERING OUR PROGRAMS. 1931 01:15:44,560 --> 01:15:50,560 IN THE SPIRIT OF OUR MOUs, A 1932 01:15:50,560 --> 01:15:54,120 PROGRAM WITH THE UNIVERSITY OF 1933 01:15:54,120 --> 01:15:58,240 WISCONSIN USING AN EXISTING 1934 01:15:58,240 --> 01:15:59,400 POPULATION OF QUIET OWNED 1935 01:15:59,400 --> 01:16:01,880 ANIMALS, THERE BY REDUCING USE 1936 01:16:01,880 --> 01:16:04,400 OF OUR ANIMALS IN RESEARCH. 1937 01:16:04,400 --> 01:16:05,600 DO YOU HAVE ANY QUESTIONS? 1938 01:16:05,600 --> 01:16:07,560 I KNOW THIS IS VERY SHORT AND 1939 01:16:07,560 --> 01:16:09,960 VERY TO THE POINT AND AGAIN WE 1940 01:16:09,960 --> 01:16:15,360 ARE -- THE V.A. IS NEW AT THIS 1941 01:16:15,360 --> 01:16:16,640 BUT WE'RE GRASPING IT 1942 01:16:16,640 --> 01:16:17,000 WHOLEHEARTEDLY. 1943 01:16:17,000 --> 01:16:18,360 >>VERY EXCITING TO SEE THE 1944 01:16:18,360 --> 01:16:20,000 PROGRESS BEING MADE AT THE V.A. 1945 01:16:20,000 --> 01:16:20,920 DO WE HAVE ANY CLARIFYING 1946 01:16:20,920 --> 01:16:23,760 QUESTIONS IN THE ROOM? 1947 01:16:23,760 --> 01:16:25,960 1948 01:16:25,960 --> 01:16:27,040 OR ONLINE? 1949 01:16:27,040 --> 01:16:29,120 JUST A REMINDER TO FOLKS 1950 01:16:29,120 --> 01:16:30,320 PARTICIPATING VIA THE WEBCAST 1951 01:16:30,320 --> 01:16:32,960 THAT YOU CAN ALWAYS SUBMIT 1952 01:16:32,960 --> 01:16:34,280 QUESTIONS VIA THE ICCVAM 1953 01:16:34,280 --> 01:16:37,320 QUESTIONS E-MAIL ADDRESS THAT 1954 01:16:37,320 --> 01:16:40,400 WAS PROVIDED TO YOU VIA YOUR 1955 01:16:40,400 --> 01:16:41,560 REGISTRATION REMINDER E-MAIL AND 1956 01:16:41,560 --> 01:16:42,400 ALSO HAS BEEN DISPLAYED 1957 01:16:42,400 --> 01:16:44,880 THROUGHOUT THE COURSE OF THE 1958 01:16:44,880 --> 01:16:45,760 MEETING. 1959 01:16:45,760 --> 01:16:48,560 OKAY. 1960 01:16:48,560 --> 01:16:57,920 NOW WE WILL MOVE ON TO OUR NEXT 1961 01:16:57,920 --> 01:17:00,280 PRESENTATION. 1962 01:17:00,280 --> 01:17:06,680 1963 01:17:06,680 --> 01:17:10,800 1964 01:17:10,800 --> 01:17:14,080 1965 01:17:14,080 --> 01:17:14,560 OKAY. 1966 01:17:14,560 --> 01:17:17,920 I'M NICOLE KLEINSTREUER. 1967 01:17:17,920 --> 01:17:21,520 I HAVE THE PRIVILEGE OF BEING 1968 01:17:21,520 --> 01:17:23,040 DIRECTOR OF THE NTP INTERAGENCY 1969 01:17:23,040 --> 01:17:25,920 CENTER FOR EVALUATION OF 1970 01:17:25,920 --> 01:17:26,680 ALTERNATIVE TOXICOLOGICAL 1971 01:17:26,680 --> 01:17:27,400 METHODS, NICEATM. 1972 01:17:27,400 --> 01:17:30,200 IT'S EVEN HARD FOR ME TO SAY, 1973 01:17:30,200 --> 01:17:31,280 AND EXECUTIVE DIRECTOR OF 1974 01:17:31,280 --> 01:17:33,800 ICCVAM. 1975 01:17:33,800 --> 01:17:35,240 TODAY I WILL GIVE A 1976 01:17:35,240 --> 01:17:38,040 PRESENTATION, FIRST HALF IS 1977 01:17:38,040 --> 01:17:40,280 GOING TO FOCUS ON NAMs WORK 1978 01:17:40,280 --> 01:17:43,880 THAT'S ONGOING AT THE NIEHS 1979 01:17:43,880 --> 01:17:47,600 DIVISION OF TRANSLATIONAL 1980 01:17:47,600 --> 01:17:48,160 TOXICOLOGY, NIEHS PRINCIPAL 1981 01:17:48,160 --> 01:17:50,520 REPRESENTATIVE IS IN THE BRITISH 1982 01:17:50,520 --> 01:17:51,240 VIRGIN ISLANDS, WARREN CASEY 1983 01:17:51,240 --> 01:17:52,600 CAN'T BE HERE TO GIVE THIS PART 1984 01:17:52,600 --> 01:17:54,360 OF THE PRESENTATION SO I'M DOING 1985 01:17:54,360 --> 01:17:55,440 DOUBLE DUTY HERE. 1986 01:17:55,440 --> 01:17:58,640 THE SECOND HALF IS GOING TO TALK 1987 01:17:58,640 --> 01:18:00,280 ABOUT SOME EFFORTS, RECENT 1988 01:18:00,280 --> 01:18:01,800 UPDATES ON ACTIVITIES THAT 1989 01:18:01,800 --> 01:18:02,800 NICEATM HAS ONGOING IN ADDITION 1990 01:18:02,800 --> 01:18:05,640 TO GREAT WORK THAT YOU HEARD 1991 01:18:05,640 --> 01:18:11,240 ABOUT YET FROM KAMEL MANSOURI IN 1992 01:18:11,240 --> 01:18:13,880 COMPUTATIONAL TOOLS SPACE. 1993 01:18:13,880 --> 01:18:15,680 THE DIVISION OF TRANSLATIONAL 1994 01:18:15,680 --> 01:18:17,120 TOXICOLOGY AT NIEHS HAS FOUR 1995 01:18:17,120 --> 01:18:20,200 PROGRAM AREAS, EXPOSURE BASED 1996 01:18:20,200 --> 01:18:20,960 RESEARCH, HEALTH EFFECTS 1997 01:18:20,960 --> 01:18:21,920 INNOVATIONS, RESPONSIVE RESEARCH 1998 01:18:21,920 --> 01:18:24,920 PROGRAMS, AND PROGRAMS IN 1999 01:18:24,920 --> 01:18:25,880 STRENGTHENING CAPABILITIES LIKE 2000 01:18:25,880 --> 01:18:28,280 SCIENTIFIC CYBER INFRASTRUCTURE. 2001 01:18:28,280 --> 01:18:31,360 THESE PROGRAMS TOGETHER TRY TO 2002 01:18:31,360 --> 01:18:32,440 COLLABORATIVELY ADDRESS PUBLIC 2003 01:18:32,440 --> 01:18:34,760 HEALTH CHALLENGES, AND GENERATE 2004 01:18:34,760 --> 01:18:36,400 TRUSTED SCIENTIFIC NFC TO 2005 01:18:36,400 --> 01:18:37,920 SUPPORT DECISION MAKING 2006 01:18:37,920 --> 01:18:39,680 PARTICULARLY BY OUR REGULATORY 2007 01:18:39,680 --> 01:18:41,440 COLLEAGUES, AND ARE FOCUSED ON 2008 01:18:41,440 --> 01:18:43,840 DEVELOPING AND APPLYING 2009 01:18:43,840 --> 01:18:44,600 INNOVATIVE TOOLS AND STRATEGIES, 2010 01:18:44,600 --> 01:18:46,800 AND I WISH THAT I HAD TIME TO 2011 01:18:46,800 --> 01:18:48,560 NAME EVERY PERSON IN THIS PHOTO 2012 01:18:48,560 --> 01:18:49,680 BECAUSE THEY HAVE CONTRIBUTED 2013 01:18:49,680 --> 01:18:50,840 TREMENDOUSLY TO THE WORK THAT 2014 01:18:50,840 --> 01:18:52,800 I'M GOING TO SHOW TODAY, IN THE 2015 01:18:52,800 --> 01:18:54,200 NEXT COUPLE SLIDES. 2016 01:18:54,200 --> 01:18:55,440 BUT THAT'S ONE OF OUR MORE 2017 01:18:55,440 --> 01:18:58,280 RECENT GROUP PHOTOS FROM THE END 2018 01:18:58,280 --> 01:18:59,160 OF 2019, AND ON THE RIGHT-HAND 2019 01:18:59,160 --> 01:19:02,560 SIDE YOU CAN SEE THE 2020 01:19:02,560 --> 01:19:03,320 TRANSLATIONAL TOXICOLOGY 2021 01:19:03,320 --> 01:19:05,160 PIPELINE, SO THIS IS THE PREMISE 2022 01:19:05,160 --> 01:19:08,120 OF HOW WE OPERATE ACROSS MANY 2023 01:19:08,120 --> 01:19:09,640 PROJECTS, SO BRINGING ALL THE 2024 01:19:09,640 --> 01:19:12,840 TOOLS IN THE TOOLBOX TO BEAR ON 2025 01:19:12,840 --> 01:19:14,840 TACKLING DIFFICULT PUBLIC HEALTH 2026 01:19:14,840 --> 01:19:16,360 CHALLENGES AND THAT OBVIOUSLY 2027 01:19:16,360 --> 01:19:17,440 INCLUDES SOME DEGREE OF ANIMAL 2028 01:19:17,440 --> 01:19:20,280 MODELS BUT ALSO INCLUDES A 2029 01:19:20,280 --> 01:19:21,360 TREMENDOUS AMOUNT OF NAMs FROM 2030 01:19:21,360 --> 01:19:23,240 COMPLEX IN VITRO SYSTEMS TO 2031 01:19:23,240 --> 01:19:25,280 HIGH-THROUGHPUT SCREENING UNDER 2032 01:19:25,280 --> 01:19:26,840 THE TOX21 PROGRAM, COMPUTATIONAL 2033 01:19:26,840 --> 01:19:29,720 ANALYSES, SYSTEM THE AIC 2034 01:19:29,720 --> 01:19:39,920 REVIEWS, 2035 01:19:41,920 --> 01:19:46,440 REVIEWS. 2036 01:19:46,440 --> 01:19:49,160 THE DNT HEI TO EVALUATE RISK TO 2037 01:19:49,160 --> 01:19:50,920 DEVELOPING NERVOUS SYSTEM. 2038 01:19:50,920 --> 01:19:56,920 SO IN COORDINATION WITH OUR EPA 2039 01:19:56,920 --> 01:20:02,960 COLLEAGUES, WITH COLLEAGUES AT 2040 01:20:02,960 --> 01:20:05,720 OECD, STRATEGY ENCOMPASSES 2041 01:20:05,720 --> 01:20:06,800 APPROACHES, IN VITRO INCLUDES 2042 01:20:06,800 --> 01:20:09,440 ASSAYS THAT COVER KEY PROCESSES 2043 01:20:09,440 --> 01:20:12,040 OF NEURODEVELOPMENT AND WE HEARD 2044 01:20:12,040 --> 01:20:13,160 YESTERDAY ABOUT OECD GUIDANCE 2045 01:20:13,160 --> 01:20:14,560 DOCUMENT THAT WAS RECENTLY 2046 01:20:14,560 --> 01:20:18,680 APPROVED BY THE WNT AND 2047 01:20:18,680 --> 01:20:19,760 PUBLISHED LATER THIS SUMMER. 2048 01:20:19,760 --> 01:20:21,160 DNT IN VITRO BATTERY IS USED TO 2049 01:20:21,160 --> 01:20:26,720 TEST A NUMBER OF CHEMICALS, 2050 01:20:26,720 --> 01:20:27,720 CRITERIA HIGHLIGHTED ON THE 2051 01:20:27,720 --> 01:20:31,880 SLIDE IN THE BLUE BOX, AND PHASE 2052 01:20:31,880 --> 01:20:33,080 1 COMPRISED OF 115 CHEMICALS 2053 01:20:33,080 --> 01:20:35,280 THAT TESTING HAS BEEN FINALIZED, 2054 01:20:35,280 --> 01:20:37,560 DATA ANALYSIS HAS ALSO BEEN 2055 01:20:37,560 --> 01:20:38,880 DONE, AND MANUSCRIPT IN 2056 01:20:38,880 --> 01:20:39,560 PREPARATION. 2057 01:20:39,560 --> 01:20:42,040 AND PHASE 2 IS ADDITIONAL 100 2058 01:20:42,040 --> 01:20:44,440 CHEMICALS SENT OUT FOR TESTING 2059 01:20:44,440 --> 01:20:47,520 TO THE VARIOUS CONTRACT LABS. 2060 01:20:47,520 --> 01:20:50,880 THE NEXT HEI PROGRAM IS FOCUSED 2061 01:20:50,880 --> 01:20:53,960 ON CARCINOGENESIS AND FOCUSED ON 2062 01:20:53,960 --> 01:20:56,680 TRYING TO DEVELOP A PROGRAM 2063 01:20:56,680 --> 01:20:58,040 AROUND TRANSLATIONAL HUMAN 2064 01:20:58,040 --> 01:20:59,480 RESEARCH, SO DDT PARTNERED WITH 2065 01:20:59,480 --> 01:21:02,600 DEPARTMENT OF DEFENSE WHICH HAS 2066 01:21:02,600 --> 01:21:06,640 A TREMENDOUS RESOURCE IN THEIR 2067 01:21:06,640 --> 01:21:08,640 SERUM REPOSITORY, OVER 70 2068 01:21:08,640 --> 01:21:10,080 MILLION SAMPLES FROM SERVICE 2069 01:21:10,080 --> 01:21:15,400 MEMBERS SINCE THE LATE 198 0s, 2070 01:21:15,400 --> 01:21:16,400 LONGITUDINAL SAMPLE, BEGINNING 2071 01:21:16,400 --> 01:21:17,600 WHEN THEY ENLIST AND COLLECTED 2072 01:21:17,600 --> 01:21:18,960 EVERY YEAR DURING TERM OF 2073 01:21:18,960 --> 01:21:19,320 SERVICE. 2074 01:21:19,320 --> 01:21:20,920 THOSE CAN BE PAIRED WITH HEALTH 2075 01:21:20,920 --> 01:21:23,000 RECORDS FROM THE SERVICE MEMBERS 2076 01:21:23,000 --> 01:21:25,280 AND FROM THINGS LIKE KNOWN 2077 01:21:25,280 --> 01:21:26,480 EXPOSURES BASED ON ENVIRONMENTS 2078 01:21:26,480 --> 01:21:29,560 THEY WERE WORKING IN OR SERVING 2079 01:21:29,560 --> 01:21:30,160 IN. 2080 01:21:30,160 --> 01:21:36,880 SO USING NOVEL OMICS APPROACHES 2081 01:21:36,880 --> 01:21:38,880 LIKE PROTEOMICS, METABOLOMICS, 2082 01:21:38,880 --> 01:21:41,840 TO UNDERSTAND BETWEEN EXPOSURES 2083 01:21:41,840 --> 01:21:42,720 AND PRE-NEOPLASTIC PATHOBIOLOGY 2084 01:21:42,720 --> 01:21:46,120 ALL THE WAY TO DISEASE OUTCOMES 2085 01:21:46,120 --> 01:21:49,480 IN THE CANCER SPACE. 2086 01:21:49,480 --> 01:21:52,520 THE NEXT PROGRAM IS THE 2087 01:21:52,520 --> 01:21:53,880 CARDIOVASCULAR HEI, AND THIS IS 2088 01:21:53,880 --> 01:21:55,840 TRYING TO UNDERSTAND THE 2089 01:21:55,840 --> 01:21:57,240 CONTRIBUTIONS OF ENVIRONMENTAL 2090 01:21:57,240 --> 01:21:59,040 CHEMICAL EXPOSURES TO 2091 01:21:59,040 --> 01:22:02,440 CARDIOVASCULAR RISK ACROSS THE 2092 01:22:02,440 --> 01:22:03,320 POPULATION. 2093 01:22:03,320 --> 01:22:04,040 AND ALONG TRANSLATIONAL 2094 01:22:04,040 --> 01:22:06,320 TOXICOLOGY PIPELINE WE HAVE 2095 01:22:06,320 --> 01:22:07,440 NAMs APPROACHES BEING 2096 01:22:07,440 --> 01:22:08,960 DEVELOPED AND APPLIED TO 2097 01:22:08,960 --> 01:22:10,160 UNDERSTANDING CARDIOVASCULAR 2098 01:22:10,160 --> 01:22:12,120 RISK. 2099 01:22:12,120 --> 01:22:14,440 ONE OF THEM IS SYSTEMATIC 2100 01:22:14,440 --> 01:22:16,520 EVIDENCE MAP TO LOOK IT THE THE 2101 01:22:16,520 --> 01:22:17,920 BODY OF EVIDENCE CONNECTING 2102 01:22:17,920 --> 01:22:19,920 CHEMICAL EXPOSURE TO 2103 01:22:19,920 --> 01:22:21,120 CARDIOVASCULAR EFFECTS, AND THAT 2104 01:22:21,120 --> 01:22:23,160 IS IN THE FINAL STAGES AND IS 2105 01:22:23,160 --> 01:22:24,960 BEING DEVELOPED AND WRITTEN FOR 2106 01:22:24,960 --> 01:22:27,880 PUBLICATION, IT'S A VERY COOL 2107 01:22:27,880 --> 01:22:28,800 INTERACTIVE TABLEAU DASHBOARD 2108 01:22:28,800 --> 01:22:31,200 WHERE YOU CAN LOOK AT DIFFERENT 2109 01:22:31,200 --> 01:22:32,840 TYPES OF EXPOSURES, LINES OF 2110 01:22:32,840 --> 01:22:35,840 EVIDENCE, IN VIVO, IN VITRO, 2111 01:22:35,840 --> 01:22:36,400 HUMAN EPIDEMIOLOGICAL AND 2112 01:22:36,400 --> 01:22:39,520 UNDERSTAND WHAT IS THE BODY OF 2113 01:22:39,520 --> 01:22:40,880 EVIDENCE CONNECTING CERTAIN 2114 01:22:40,880 --> 01:22:42,600 EXOGENOUS EXPOSURES TO DIFFERENT 2115 01:22:42,600 --> 01:22:43,120 CARDIOVASCULAR ENDPOINTS. 2116 01:22:43,120 --> 01:22:47,000 AND THEN WE HAVE A WHOLE PROGRAM 2117 01:22:47,000 --> 01:22:48,720 AROUND COMPUTATIONAL MODELING OF 2118 01:22:48,720 --> 01:22:49,360 CARDIOVASCULAR RISK SO 2119 01:22:49,360 --> 01:22:50,560 INTEGRATING HIGH-THROUGHPUT 2120 01:22:50,560 --> 01:22:53,680 SCREENING DATA FROM TOX21 2121 01:22:53,680 --> 01:22:58,240 PROGRAM, MAPPING THAT TO TWO 2122 01:22:58,240 --> 01:22:58,760 CARDIOVASCULAR ENDPOINTS, 2123 01:22:58,760 --> 01:23:07,240 MOLECULAR AND CELLULAR LEVEL. 2124 01:23:07,240 --> 01:23:11,160 THE COMBINED EXPOSURES AND 2125 01:23:11,160 --> 01:23:13,160 MIXTURES PROGRAM IS A 2126 01:23:13,160 --> 01:23:15,480 PARTNERSHIP WITH BOTANICAL 2127 01:23:15,480 --> 01:23:17,960 SAFETY CONSORTIUM SO THIS 2128 01:23:17,960 --> 01:23:21,240 INCLUDES NIEHS, FDA, AND HEFI, 2129 01:23:21,240 --> 01:23:23,320 AN INDUSTRY CONSORTIUM, THERE'S 2130 01:23:23,320 --> 01:23:27,920 OVER 150 MEMBERS FROM ACADEMIA, 2131 01:23:27,920 --> 01:23:29,200 GOVERNMENT, INDUSTRY LOOKING AT 2132 01:23:29,200 --> 01:23:32,080 SUIT BUILT OF NAM-BASED TOXICITY 2133 01:23:32,080 --> 01:23:34,160 ASSAYS TO ASSESS THE POTENTIAL 2134 01:23:34,160 --> 01:23:40,040 TOXICITY OR RISK OF COMPLEX 2135 01:23:40,040 --> 01:23:40,720 MIXTURES OF BOTANICAL 2136 01:23:40,720 --> 01:23:41,840 INGREDIENTS, TECHNICAL WORKING 2137 01:23:41,840 --> 01:23:44,040 GROUPS WITH EXPERTISE IN EACH 2138 01:23:44,040 --> 01:23:45,560 PRIOR AREA, TO IDENTIFY 2139 01:23:45,560 --> 01:23:46,880 BOTANICAL INGREDIENTS AND ASSAYS 2140 01:23:46,880 --> 01:23:48,440 THAT MIGHT BE APPROPRIATE FOR 2141 01:23:48,440 --> 01:23:53,120 TESTING THOSE INGREDIENTS AND 2142 01:23:53,120 --> 01:23:54,760 EVALUATING TOXICITIES, END GOAL 2143 01:23:54,760 --> 01:23:55,720 TO DEVELOP COMPREHENSIVE 2144 01:23:55,720 --> 01:23:58,720 FRAMEWORK AND TOOLBOX FOR 2145 01:23:58,720 --> 01:23:59,800 EVALUATING SAFETY OF OF 2146 01:23:59,800 --> 01:24:00,760 BOTANICALS, IDENTIFYING ASSAYS 2147 01:24:00,760 --> 01:24:02,640 READY FOR PRIME TIME, THOSE 2148 01:24:02,640 --> 01:24:04,520 AREAS THAT NEED FURTHER 2149 01:24:04,520 --> 01:24:05,280 DEVELOPMENT, AND EVENTUALLY 2150 01:24:05,280 --> 01:24:12,080 EXTEND THE TOOLBOX BEYOND 2151 01:24:12,080 --> 01:24:12,400 BOTANICALS. 2152 01:24:12,400 --> 01:24:13,000 OCCUPATIONAL EXPOSURES PROGRAM 2153 01:24:13,000 --> 01:24:16,880 AT THE DIVISION OF TRANSLATIONAL 2154 01:24:16,880 --> 01:24:18,200 TOXICOLOGY IS EVALUATING 2155 01:24:18,200 --> 01:24:19,320 CAPABILITIES FOR PREDICTING 2156 01:24:19,320 --> 01:24:23,240 ADVERSE HEALTH EFFECTS IN THE 2157 01:24:23,240 --> 01:24:23,800 INHALATION TOXICOLOGY SPACE, 2158 01:24:23,800 --> 01:24:25,680 LOOKING AT A NUMBER OF NAMs 2159 01:24:25,680 --> 01:24:29,560 THAT COVER DIFFERENT IN VITRO 2160 01:24:29,560 --> 01:24:30,120 MODELS AND MICROPHYSIOLOGIC 2161 01:24:30,120 --> 01:24:35,280 SYSTEMS LIKE LUNG ON A CLIP TO 2162 01:24:35,280 --> 01:24:36,800 EVALUATE HUMAN RESPIRATORY 2163 01:24:36,800 --> 01:24:42,280 TOXICITY USING HUMAN CELL-BASED 2164 01:24:42,280 --> 01:24:47,080 APPROACHES, ONE IS AIR-LIQUID 2165 01:24:47,080 --> 01:24:49,920 INTERFACE, USING HUMAN DERIVED 2166 01:24:49,920 --> 01:24:51,680 PRIMARY AIRWAY CELLS TO TEST 2167 01:24:51,680 --> 01:24:54,000 CHEMICAL EXPOSURES IN HUMAN 2168 01:24:54,000 --> 01:24:55,880 RELEVANT SYSTEM AND DO THINGS 2169 01:24:55,880 --> 01:24:58,280 LIKE UNDERSTAND DIVERSITY OF 2170 01:24:58,280 --> 01:25:00,320 RESPONSE ACROSS HETEROGENEOUS 2171 01:25:00,320 --> 01:25:01,520 POPULATION BY USING MULTIPLE 2172 01:25:01,520 --> 01:25:03,520 DONORS AND LOOKING AT THE 2173 01:25:03,520 --> 01:25:05,520 VARIABILITY OF THAT RESPONSE AND 2174 01:25:05,520 --> 01:25:06,680 SENSITIVITY OF THOSE RESPONSES. 2175 01:25:06,680 --> 01:25:12,360 AT THE MOMENT, THERE'S A STUDY 2176 01:25:12,360 --> 01:25:20,480 IN PROGRESS LOOKING AT 2, 2177 01:25:20,480 --> 01:25:23,520 3-PENTANEDION VAPORS, ARTIFICIAL 2178 01:25:23,520 --> 01:25:26,400 BUTTER FLAVOR IN POPCORN, 2179 01:25:26,400 --> 01:25:31,400 ADVERSE EFFECT IN WORKERS IN 2180 01:25:31,400 --> 01:25:32,040 FACTORIES. 2181 01:25:32,040 --> 01:25:35,760 AND THE FIRST AREA FOCUSED ON 2182 01:25:35,760 --> 01:25:38,400 HERE IS TRYING TO IMPROVE AND 2183 01:25:38,400 --> 01:25:40,520 UPDATE METHODS AROUND APPROACHES 2184 01:25:40,520 --> 01:25:42,040 TO CLUSTERING AND CLASSIFICATION 2185 01:25:42,040 --> 01:25:44,320 OF COMPOUNDS, BASED ON 2186 01:25:44,320 --> 01:25:47,160 STRUCTURES, SO LOOKING AT REALLY 2187 01:25:47,160 --> 01:25:50,440 BEST PRACTICES AROUND DEFINING 2188 01:25:50,440 --> 01:25:51,800 CONCEPTS OF STRUCTURAL 2189 01:25:51,800 --> 01:25:58,000 SIMILARITY USING SUPERVISED AND 2190 01:25:58,000 --> 01:26:03,800 UNSUPERVISED APPROACHES. 2191 01:26:03,800 --> 01:26:06,120 THERE WAS A WORKSHOP, KAMEL 2192 01:26:06,120 --> 01:26:12,280 MANSOURI, LAST YEAR, SCAN THE QR 2193 01:26:12,280 --> 01:26:13,440 CODE, HOW TO DEFINE SIMILARITY 2194 01:26:13,440 --> 01:26:15,960 IN A GENERAL WAY BUT REALLY IN 2195 01:26:15,960 --> 01:26:17,360 AN ENDPOINT-SPECIFIC WAY. 2196 01:26:17,360 --> 01:26:18,800 SO THINKING ABOUT ENDPOINT THAT 2197 01:26:18,800 --> 01:26:20,360 YOU'RE TRYING TO PREDICT OR 2198 01:26:20,360 --> 01:26:21,840 UNDERSTAND AND LOOKING AT 2199 01:26:21,840 --> 01:26:23,760 SIMILARITY WITH RESPECT TO THAT 2200 01:26:23,760 --> 01:26:24,880 PARTICULAR ENDPOINT AND THERE'S 2201 01:26:24,880 --> 01:26:25,920 A WORKSHOP REPORT BEING WRITTEN 2202 01:26:25,920 --> 01:26:29,000 UP FOR THAT RIGHT NOW. 2203 01:26:29,000 --> 01:26:31,400 AND THEN CPT PROGRAM ALSO DOES A 2204 01:26:31,400 --> 01:26:33,160 LOT OF SYSTEMATIC EVIDENCE 2205 01:26:33,160 --> 01:26:34,680 MAPPING SIMILAR TO WHAT I 2206 01:26:34,680 --> 01:26:35,880 DESCRIBED FOR CARDIOVASCULAR HEI 2207 01:26:35,880 --> 01:26:39,320 TEAM AND WE WORK CLOSELY WITH -- 2208 01:26:39,320 --> 01:26:40,720 ACROSS MEMBERS OF THE DIFFERENT 2209 01:26:40,720 --> 01:26:42,920 TEAMS TO APPLY BEST PRACTICES 2210 01:26:42,920 --> 01:26:44,640 AND APPROACHES TO DOING 2211 01:26:44,640 --> 01:26:45,320 SYSTEMATIC EVIDENCE MAPPING AND 2212 01:26:45,320 --> 01:26:49,760 THEY HAVE ONE RIGHT NOW LOOKING 2213 01:26:49,760 --> 01:26:53,960 AT ORGANOPHOSPATE FLAME 2214 01:26:53,960 --> 01:26:55,160 RETARDANTS, PERSONAL CARE 2215 01:26:55,160 --> 01:26:58,320 PRODUCTS AND EFFECT ON PUBERTY 2216 01:26:58,320 --> 01:26:59,440 AND FETAL DEVELOPMENT, 2217 01:26:59,440 --> 01:27:00,280 DEVELOPING TREMENDOUS RESOURCES 2218 01:27:00,280 --> 01:27:00,960 THERE. 2219 01:27:00,960 --> 01:27:05,440 OTHER WORK AT OTHER PMTs, 2220 01:27:05,440 --> 01:27:07,960 SCIENTIFIC CYBER INFRASTRUCTURE 2221 01:27:07,960 --> 01:27:11,880 PMT, INCLUDES CHARLES SCHMITT 2222 01:27:11,880 --> 01:27:14,320 AND JENNIFER FOSTEELL LEADING 2223 01:27:14,320 --> 01:27:15,760 EFFORTS TO MAKE THE VALUABLE 2224 01:27:15,760 --> 01:27:17,720 DATA THE DIVISION OF 2225 01:27:17,720 --> 01:27:19,120 TRANSLATIONAL TOXICOLOGY AND 2226 01:27:19,120 --> 01:27:19,960 BROADER NATIONAL TOXICOLOGY 2227 01:27:19,960 --> 01:27:21,880 PROGRAM HAVE PRODUCED OVER THE 2228 01:27:21,880 --> 01:27:23,280 LAST SEVERAL DECADES, MAKING 2229 01:27:23,280 --> 01:27:23,960 THAT ACCESSIBLE. 2230 01:27:23,960 --> 01:27:26,880 SO I'M SURE MANY OF YOU HAVE 2231 01:27:26,880 --> 01:27:30,000 HEARD OF FAIR PRINCIPLES, DATA 2232 01:27:30,000 --> 01:27:33,120 OBJECTS AND DATA RESOURCES 2233 01:27:33,120 --> 01:27:34,360 SHOULD BE FINDABLE, ACCESSIBLE, 2234 01:27:34,360 --> 01:27:35,640 INTEROPERABLE, REUSABLE, THAT 2235 01:27:35,640 --> 01:27:38,040 MEANS THEY ARE RESOURCES THAT 2236 01:27:38,040 --> 01:27:39,280 SHOULD BE UNDERSTANDABLE BY 2237 01:27:39,280 --> 01:27:40,200 HUMANS AND MACHINES IN A WAY 2238 01:27:40,200 --> 01:27:42,000 THAT ALLOWS THEM TO BE COMBINED 2239 01:27:42,000 --> 01:27:44,280 INTO LARGE SUPER SETS OF DATA 2240 01:27:44,280 --> 01:27:47,040 USED TO BUILD AND TRAIN MODELS, 2241 01:27:47,040 --> 01:27:48,680 TO VALIDATE NEW APPROACHES, ET 2242 01:27:48,680 --> 01:27:49,120 CETERA. 2243 01:27:49,120 --> 01:27:52,760 AND SO CHARLES AND JENNIFER ARE 2244 01:27:52,760 --> 01:27:54,720 LEADING EFFORTS TO EFFORTS DTT 2245 01:27:54,720 --> 01:27:57,680 DATA DICTIONARIES, TO USE OUR 2246 01:27:57,680 --> 01:27:58,880 IN-HOUSE ONTOLOGICAL EXPERTISE 2247 01:27:58,880 --> 01:28:04,480 TO APPLY THINGS LIKE CONTROLLED 2248 01:28:04,480 --> 01:28:05,880 VOCABULARIES, STANDARDIZED 2249 01:28:05,880 --> 01:28:08,080 TERMINOLOGIES WITH SUBGROUPS 2250 01:28:08,080 --> 01:28:09,280 LIKE KNOWLEDGE MANAGEMENT TEAM 2251 01:28:09,280 --> 01:28:10,720 COLLABORATING WITH FEDERAL 2252 01:28:10,720 --> 01:28:12,800 PARTNERS LIKE EPA AND ENGAGING 2253 01:28:12,800 --> 01:28:15,320 WITH OTHER ONTOLOGY COMMUNITIES 2254 01:28:15,320 --> 01:28:17,680 AND OUR NIEHS GRANTEES. 2255 01:28:17,680 --> 01:28:20,560 ONE SPECIFIC EXAMPLE IS THE 2256 01:28:20,560 --> 01:28:22,120 ENVIRONMENTAL HEALTH LANGUAGE 2257 01:28:22,120 --> 01:28:25,120 COLLABORATIVE, THEIR MISSION IS 2258 01:28:25,120 --> 01:28:26,920 TO PROMOTE INTEROPERABLE 2259 01:28:26,920 --> 01:28:28,240 TERMINOLOGIES AND BEST PRACTICES 2260 01:28:28,240 --> 01:28:29,640 AROUND CREATING FAIR DATASETS 2261 01:28:29,640 --> 01:28:32,800 SUCH THAT WE CAN LEVERAGE THE 2262 01:28:32,800 --> 01:28:34,000 WEALTH OF DATA AVAILABLE TO US 2263 01:28:34,000 --> 01:28:41,440 IN A WAY THAT ALLOWS FOR 2264 01:28:41,440 --> 01:28:42,240 STANDARDIZEIZATION AND 2265 01:28:42,240 --> 01:28:43,760 UTILIZATION ACROSS APPLICATIONS. 2266 01:28:43,760 --> 01:28:45,320 IF YOU'RE INTERESTED CONTACT 2267 01:28:45,320 --> 01:28:46,840 STEPHANIE HOLMGREN AT THE DTT. 2268 01:28:46,840 --> 01:28:48,680 AND YOU CAN SEE A NUMBER OF 2269 01:28:48,680 --> 01:28:51,200 DIFFERENT USE CASES THAT ARE 2270 01:28:51,200 --> 01:28:52,720 BRIG LED BY EHLC COLLABORATORS 2271 01:28:52,720 --> 01:28:56,000 AT OUR FEDERAL AGENCY PARTNERS 2272 01:28:56,000 --> 01:28:58,440 LIKE EPA BUT ALSO ACADEMIC 2273 01:28:58,440 --> 01:29:00,640 PARTNERS LIKE HARVARD AND 2274 01:29:00,640 --> 01:29:02,360 COLUMBIA TO ANSWER QUESTIONS, 2275 01:29:02,360 --> 01:29:04,200 YOU KNOW, FAIRLY BASIC QUESTIONS 2276 01:29:04,200 --> 01:29:07,080 LIKE WHAT DATA EXIST FOR A GIVEN 2277 01:29:07,080 --> 01:29:08,200 EXPOSURE SCENARIO, GIVEN 2278 01:29:08,200 --> 01:29:09,480 CHEMICAL EXPOSURE, HOW DOES THAT 2279 01:29:09,480 --> 01:29:11,760 RELATE TO AN ENDPOINT, HOW CAN 2280 01:29:11,760 --> 01:29:13,640 WE COMPILE RELEVANT DATA IN A 2281 01:29:13,640 --> 01:29:17,680 WAY THAT IS FAIR AND ACCESSIBLE. 2282 01:29:17,680 --> 01:29:23,800 THAT WAS A WHIRLWIND TOUR OF 2283 01:29:23,800 --> 01:29:26,440 NAMs AT DTT. 2284 01:29:26,440 --> 01:29:28,520 I'LL SWITCH GEARS AND TALK ABOUT 2285 01:29:28,520 --> 01:29:30,720 WORK NICEATM IS DOING IN SUPPORT 2286 01:29:30,720 --> 01:29:31,480 OF ICCVAM. 2287 01:29:31,480 --> 01:29:34,200 SO NICEATM IS ALSO A PART OF THE 2288 01:29:34,200 --> 01:29:36,080 DIVISION OF TRANSLATIONAL 2289 01:29:36,080 --> 01:29:37,760 TOXICOLOGY, AND WE WORK CLOSELY 2290 01:29:37,760 --> 01:29:39,480 WITH ALL OF THE PROGRAM 2291 01:29:39,480 --> 01:29:40,240 MANAGEMENT TEAMS THAT I 2292 01:29:40,240 --> 01:29:42,400 MENTIONED IN THE LAST TEN SLIDES 2293 01:29:42,400 --> 01:29:45,480 OR SO. 2294 01:29:45,480 --> 01:29:47,040 BUT OUR PRIMARY RESPONSIBILITY 2295 01:29:47,040 --> 01:29:49,760 IS TO FULFILL OUR CONGRESSIONAL 2296 01:29:49,760 --> 01:29:51,960 MANDATE TO PROVIDE SUPPORT TO 2297 01:29:51,960 --> 01:29:52,920 THE INTERAGENCY COORDINATING 2298 01:29:52,920 --> 01:29:56,880 COMMITTEE FOR VALIDATION OF 2299 01:29:56,880 --> 01:29:57,520 ALTERNATIVE METHODS, ICCVAM, 17 2300 01:29:57,520 --> 01:29:58,400 FEDERAL AGENCIES. 2301 01:29:58,400 --> 01:30:01,040 WE HAVE A VERY BROAD PORTFOLIO 2302 01:30:01,040 --> 01:30:01,720 OF WORK. 2303 01:30:01,720 --> 01:30:03,680 I WON'T HAVE THE OPPORTUNITY TO 2304 01:30:03,680 --> 01:30:05,720 TALK ABOUT EVERY SINGLE ONE OF 2305 01:30:05,720 --> 01:30:07,280 THESE BULLETED ITEMS TODAY BUT 2306 01:30:07,280 --> 01:30:08,920 IF YOU'RE INTERESTED IN ANY 2307 01:30:08,920 --> 01:30:09,920 SPECIFIC TOPIC AREA PLEASE 2308 01:30:09,920 --> 01:30:11,760 FOLLOW UP WITH ME, I'M ALWAYS 2309 01:30:11,760 --> 01:30:13,280 DELIGHTED TO TALK OFFLINE ABOUT 2310 01:30:13,280 --> 01:30:14,600 WORK WE'RE DOING. 2311 01:30:14,600 --> 01:30:16,360 I ALSO HOPE THAT MOST OF YOU WHO 2312 01:30:16,360 --> 01:30:17,560 FOUND YOUR WAY HERE TODAY IN 2313 01:30:17,560 --> 01:30:19,640 PERSON OR ON THE WEBCAST ARE 2314 01:30:19,640 --> 01:30:21,200 ALREADY SUBSCRIBED TO THE 2315 01:30:21,200 --> 01:30:23,480 NICEATM NEWS E-MAIL LIST, BUT IF 2316 01:30:23,480 --> 01:30:24,880 YOU'RE NOT SCAN THE QR CODE OR 2317 01:30:24,880 --> 01:30:26,920 GO TO THE LINK AND MAKE SURE YOU 2318 01:30:26,920 --> 01:30:28,400 GET SUBSCRIBED TO THE 2319 01:30:28,400 --> 01:30:28,880 NEWSLETTER. 2320 01:30:28,880 --> 01:30:31,120 IT COMES OUT ALMOST WEEKLY AND 2321 01:30:31,120 --> 01:30:33,520 PROVIDES A WEALTH OF INFORMATION 2322 01:30:33,520 --> 01:30:35,160 ABOUT DEVELOPMENTS IN THE FIELD, 2323 01:30:35,160 --> 01:30:36,920 FUNDING OPPORTUNITIES, JOB 2324 01:30:36,920 --> 01:30:43,720 OPPORTUNITIES, NEW PUBLICATION, 2325 01:30:43,720 --> 01:30:45,480 CONFERENCES, ET CETERA. 2326 01:30:45,480 --> 01:30:46,680 AND THE BIENNIAL PROGRESS REPORT 2327 01:30:46,680 --> 01:30:49,640 IS PART OF THE CONGRESSIONAL 2328 01:30:49,640 --> 01:30:52,000 MANDATE, COMES OUT EVERY TWO 2329 01:30:52,000 --> 01:30:58,040 YEARS, ONE PARAGRAPH SUMMARY OF 2330 01:30:58,040 --> 01:31:04,400 EACH ACTIVITY OF ICCVAM 2331 01:31:04,400 --> 01:31:05,920 AGENCIES, THE WORK NICEATM DOES 2332 01:31:05,920 --> 01:31:07,280 TO SUPPORT AND WORK INDIVIDUALLY 2333 01:31:07,280 --> 01:31:10,640 OR IN PARTNERSHIP WITH ONE 2334 01:31:10,640 --> 01:31:11,280 ANOTHER. 2335 01:31:11,280 --> 01:31:13,240 ONE EXAMPLE OF WORK THAT WE'VE 2336 01:31:13,240 --> 01:31:15,120 BEEN CONTINUING OVER THE LAST 2337 01:31:15,120 --> 01:31:17,320 FIVE OR SIX YEARS THAT KAMEL 2338 01:31:17,320 --> 01:31:19,520 TOUCHED ON BRIEFLY YESTERDAY IS 2339 01:31:19,520 --> 01:31:21,800 THIS APPROACH WE'VE TAKEN TO 2340 01:31:21,800 --> 01:31:23,800 GLOBAL CROWDSOURCING OF 2341 01:31:23,800 --> 01:31:26,080 PREDICTIVE MODELS. 2342 01:31:26,080 --> 01:31:27,640 THESE ARE QUANTITATIVE STRUCTURE 2343 01:31:27,640 --> 01:31:28,240 ACTIVITY RELATIONSHIP MODELS, 2344 01:31:28,240 --> 01:31:29,760 MOST PEOPLE ARE FAMILIAR BUT 2345 01:31:29,760 --> 01:31:32,280 BASIC PREMISE IF YOU HAVE ENOUGH 2346 01:31:32,280 --> 01:31:33,800 DATA ON A DIVERSE CHEMICAL SET 2347 01:31:33,800 --> 01:31:35,160 YOU CAN USE ARTIFICIAL 2348 01:31:35,160 --> 01:31:36,480 INTELLIGENCE AND MACHINE 2349 01:31:36,480 --> 01:31:37,880 LEARNING APPROACHES TO TRAIN 2350 01:31:37,880 --> 01:31:39,960 ROBUST AND RELIABLE MODELS THAT 2351 01:31:39,960 --> 01:31:41,400 IDENTIFY COMPLEX RELATIONSHIPS 2352 01:31:41,400 --> 01:31:43,040 BETWEEN CHEMICAL FEATURES LIKE 2353 01:31:43,040 --> 01:31:44,040 MOLECULAR DESCRIPTORS OR 2354 01:31:44,040 --> 01:31:45,160 PhysChem CAL PRODUCTS AND 2355 01:31:45,160 --> 01:31:47,840 ENDPOINTS THAT YOU ARE TRIAL TO 2356 01:31:47,840 --> 01:31:48,080 PREDICT. 2357 01:31:48,080 --> 01:31:55,960 OPERA IS A SUITE OF THESE MODELS 2358 01:31:55,960 --> 01:32:02,080 INCLUDING PHYSICOCHEMICAL AND 2359 01:32:02,080 --> 01:32:03,840 TOXICITY PREDICTION MODELS. 2360 01:32:03,840 --> 01:32:05,880 WE CURATED DATASETS, SHARED WITH 2361 01:32:05,880 --> 01:32:07,640 COMPUTATIONAL CHEMISTRY GROUPS 2362 01:32:07,640 --> 01:32:09,280 AROUND THE WORLD, HAD THEM 2363 01:32:09,280 --> 01:32:11,280 SUBMIT MODELS BACK ON A TRAINING 2364 01:32:11,280 --> 01:32:14,560 SET AND HOLDOUT TEST SAID WE 2365 01:32:14,560 --> 01:32:17,320 USED TO EVALUATE PERFORMANCE AND 2366 01:32:17,320 --> 01:32:18,840 COMBINED THEM USING ENSEMBLE 2367 01:32:18,840 --> 01:32:19,920 APPROACH INTO THESE CONSENSUS 2368 01:32:19,920 --> 01:32:23,320 MODELS THAT CAN BE USED TO 2369 01:32:23,320 --> 01:32:24,960 PREDICT TOXICITY ACROSS THE 2370 01:32:24,960 --> 01:32:27,800 CHEMICAL UNIVERSE WITH DEFINED 2371 01:32:27,800 --> 01:32:30,200 STRUCTURE AND ARE ROBUST AND 2372 01:32:30,200 --> 01:32:31,000 RELIABLE. 2373 01:32:31,000 --> 01:32:34,440 WE HAVE THESE FOR ENDOCRINE 2374 01:32:34,440 --> 01:32:35,320 DISRUPTION, YESTERDAY MONIQUE 2375 01:32:35,320 --> 01:32:36,840 MENTIONED A WHITE PAPER PUT OUT 2376 01:32:36,840 --> 01:32:40,280 AT THE BEGINNING OF THE YEAR, 2377 01:32:40,280 --> 01:32:43,960 REFERS TO THE MODELS FOR E.R. 2378 01:32:43,960 --> 01:32:46,880 AND A.R., ESTROGEN AND ANDROGEN 2379 01:32:46,880 --> 01:32:47,760 RECEPTOR PATHWAY PREDICTION 2380 01:32:47,760 --> 01:32:49,760 BEING ACCEPTABLE FOR WEIGHT OF 2381 01:32:49,760 --> 01:32:51,080 EVIDENCE AND PRIORITIZATION OF 2382 01:32:51,080 --> 01:32:52,320 COMPOUNDS SO EXCITING TO SEE 2383 01:32:52,320 --> 01:32:54,000 REGULATORY APPLICATION OF THOSE 2384 01:32:54,000 --> 01:32:56,360 MODELS BY THE EPA. 2385 01:32:56,360 --> 01:32:59,840 WE ALSO HAVE COLLABORATIVE ACUTE 2386 01:32:59,840 --> 01:33:01,400 TOXICITY SUITE, CATMoS, 2387 01:33:01,400 --> 01:33:04,000 PREDICTS ORAL ACUTE SYSTEMIC 2388 01:33:04,000 --> 01:33:06,720 TOXICITY, BASED ON A DATASET OF 2389 01:33:06,720 --> 01:33:08,040 10,000 CHEMICALS WITH RODENT 2390 01:33:08,040 --> 01:33:08,240 DATA. 2391 01:33:08,240 --> 01:33:11,120 ONE OF THE WAYS IN WHICH WE'VE 2392 01:33:11,120 --> 01:33:13,880 STARTED TO ENLIST EVALUATING 2393 01:33:13,880 --> 01:33:17,120 MODEL PERFORMANCE IS TRY TO 2394 01:33:17,120 --> 01:33:18,120 UNDERSTAND VARIABILITY AND 2395 01:33:18,120 --> 01:33:19,440 REPRODUCIBILITY OF OUR 2396 01:33:19,440 --> 01:33:21,160 BENCHMARKS OF OUR BASELINES. 2397 01:33:21,160 --> 01:33:23,920 SO IT STANDS TO REASON THAT YOU 2398 01:33:23,920 --> 01:33:26,200 CAN'T EXPECT A MODEL TO DO 2399 01:33:26,200 --> 01:33:28,760 BETTER AT PREDICTING AN ENDPOINT 2400 01:33:28,760 --> 01:33:30,360 THAN THAT ENDPOINT DOES AT 2401 01:33:30,360 --> 01:33:31,920 PREDICTING ITSELF, RIGHT? 2402 01:33:31,920 --> 01:33:33,640 YOUR BASELINE FOR ASSESSING 2403 01:33:33,640 --> 01:33:35,520 PERFORMANCE OF A NEW APPROACH 2404 01:33:35,520 --> 01:33:37,480 SHOULD BE THE REPRODUCIBILITY OF 2405 01:33:37,480 --> 01:33:38,160 THAT EXISTING REFERENCE 2406 01:33:38,160 --> 01:33:40,440 STANDARD, IN THIS CASE IN VIVO 2407 01:33:40,440 --> 01:33:40,840 ANIMAL TEST. 2408 01:33:40,840 --> 01:33:44,520 SO, AS PART OF THIS PROJECT WE 2409 01:33:44,520 --> 01:33:46,560 HAD INDEPENDENTLY REPLICATED IN 2410 01:33:46,560 --> 01:33:48,280 VIVO ANIMAL DATA ON A COUPLE 2411 01:33:48,280 --> 01:33:49,840 THOUSAND CHEMICALS SO WE WERE 2412 01:33:49,840 --> 01:33:52,120 ABLE TO USE STATISTICAL 2413 01:33:52,120 --> 01:33:54,320 BOOTSTRAPPING APPROACH TO BOOT 2414 01:33:54,320 --> 01:33:55,440 STRAP THROUGH STANDARD 2415 01:33:55,440 --> 01:33:57,360 DEVIATIONS AROUND LD 50s OF 2416 01:33:57,360 --> 01:33:58,560 CHEMICALS WITH REPLICATE STUDIES 2417 01:33:58,560 --> 01:34:02,840 AND USE THAT TO DERIVE A 95% 2418 01:34:02,840 --> 01:34:03,600 CONFIDENCE INTERVAL WHICH 2419 01:34:03,600 --> 01:34:08,000 EQUATES TO A QUARTER LOG, PLUS 2420 01:34:08,000 --> 01:34:10,200 OR MINUS 25, SHOWN IN THE BLUE 2421 01:34:10,200 --> 01:34:12,720 SHADING AROUND THAT DOT PLOT, 2422 01:34:12,720 --> 01:34:15,560 WHICH, YOU KNOW, SERVES AS A 2423 01:34:15,560 --> 01:34:17,920 REASONABLE RANGE FOR EVALUATING 2424 01:34:17,920 --> 01:34:20,280 ACCEPTABLE LD 50 ESTIMATE ON AS 2425 01:34:20,280 --> 01:34:21,560 CHEMICAL BY CHEMICAL BASIS 2426 01:34:21,560 --> 01:34:23,080 LOOKING AT PREDICTIONS OF NEW 2427 01:34:23,080 --> 01:34:29,760 MODELS, AND SO CATMoS QSAR 2428 01:34:29,760 --> 01:34:31,920 PREDICTIONS PERFORM JUST AS WELL 2429 01:34:31,920 --> 01:34:34,360 AS PREDICTING ORAL TOXICITY 2430 01:34:34,360 --> 01:34:35,880 OUTCOME AND YOU HEARD MONIQUE 2431 01:34:35,880 --> 01:34:38,280 MENTION YESTERDAY WE'RE WORKING 2432 01:34:38,280 --> 01:34:39,600 WITH EPA AND ECOLOGICAL EFFECTS 2433 01:34:39,600 --> 01:34:40,400 DIVISION TO EVALUATE WHETHER OR 2434 01:34:40,400 --> 01:34:43,120 NOT YOU COULD USE THE PREDICTED 2435 01:34:43,120 --> 01:34:45,160 LD 50 VALUES IN RISK ASSESSMENTS 2436 01:34:45,160 --> 01:34:47,160 AND ARRIVE AT THE SAME 2437 01:34:47,160 --> 01:34:48,840 CONCLUSIONS OR BE JUST AS 2438 01:34:48,840 --> 01:34:51,840 PROTECTIVE AS THE IN VIVO LD 50 2439 01:34:51,840 --> 01:34:53,480 VALUE, THAT MANUSCRIPT IS BEING 2440 01:34:53,480 --> 01:34:55,680 WRITTEN FOR PUBLICATION RIGHT 2441 01:34:55,680 --> 01:34:57,880 NOW. 2442 01:34:57,880 --> 01:35:02,480 OUR NEXT GLOBAL COLLABORATIVE 2443 01:35:02,480 --> 01:35:05,440 VOWED SOURCING PROJECT EXTENDS 2444 01:35:05,440 --> 01:35:11,680 TO INHALATION, LC 50, WHERE YOU 2445 01:35:11,680 --> 01:35:14,960 SEE LETHALITY IN ANIMALS AFTER 2446 01:35:14,960 --> 01:35:17,040 INHALATION EXPOSURE, WE'VE 2447 01:35:17,040 --> 01:35:21,760 LOOKED ACROSS RECURSES FROM 2448 01:35:21,760 --> 01:35:28,520 ECHA, CHEMICOIDPLUS, DEPARTMENT 2449 01:35:28,520 --> 01:35:34,120 DEFENSE, EPA, EVALUATING UNITS 2450 01:35:34,120 --> 01:35:36,000 ARE STANDARDIZES, CONVERTING, 2451 01:35:36,000 --> 01:35:39,320 DETERMINING PHASE OF EXPOSURE, 2452 01:35:39,320 --> 01:35:40,080 WHETHER GAS, VAPOR, AEROSOL, 2453 01:35:40,080 --> 01:35:44,320 WE'VE BEEN ABLE TO LEAN ON 2454 01:35:44,320 --> 01:35:46,720 OPERA, OPERA PREDICTS MELTING 2455 01:35:46,720 --> 01:35:48,480 POINT, VAPOR POINT TO PREDICT 2456 01:35:48,480 --> 01:35:50,560 PHASE OF EXPOSURE BECAUSE ONLY 2457 01:35:50,560 --> 01:35:53,080 28% OF THE STUDY REPORTS WE 2458 01:35:53,080 --> 01:35:54,400 FOUND ACTUALLY REPORT THAT 2459 01:35:54,400 --> 01:35:54,720 PHASE. 2460 01:35:54,720 --> 01:35:57,400 BUT THE LONG AND SHORT IS AFTER 2461 01:35:57,400 --> 01:35:58,360 THIS MULTI-YEAR DATA CURATION 2462 01:35:58,360 --> 01:36:00,240 PROCESS WE'VE ENDED UP WITH A 2463 01:36:00,240 --> 01:36:01,840 PRETTY ROBUST DATASET FOR THE 2464 01:36:01,840 --> 01:36:03,480 MODELING EFFORTS SO WE HAVE OVER 2465 01:36:03,480 --> 01:36:05,040 A THOUSAND UNIQUE CHEMICALS IN 2466 01:36:05,040 --> 01:36:06,560 THE DATABASE, AND WE'RE GOING TO 2467 01:36:06,560 --> 01:36:09,320 BE KICK STARTING THIS GLOBAL 2468 01:36:09,320 --> 01:36:10,600 COLLABORATIVE EFFORT SOON, KAMEL 2469 01:36:10,600 --> 01:36:12,360 WILL LEAD THAT ON OUR SIDE AS 2470 01:36:12,360 --> 01:36:12,560 WELL. 2471 01:36:12,560 --> 01:36:14,120 MOST OF YOU ARE FAMILIAR WITH 2472 01:36:14,120 --> 01:36:16,160 THE WORK THAT WE'VE DONE OVER 2473 01:36:16,160 --> 01:36:20,680 THE LAST DECADE OR SO IN SKIN 2474 01:36:20,680 --> 01:36:22,320 SENSITIZATION. 2475 01:36:22,320 --> 01:36:23,520 AND THE ACCOMPLISHMENT FROM 2021 2476 01:36:23,520 --> 01:36:26,160 OF GETTING THE FIRST EVER 2477 01:36:26,160 --> 01:36:30,720 DEFINED APPROACH GUIDELINE UNDER 2478 01:36:30,720 --> 01:36:35,920 OECD, FOR SKIN SENSITIZEIZATION, 2479 01:36:35,920 --> 01:36:37,960 MAPPING TO CELLULAR AND KEY 2480 01:36:37,960 --> 01:36:40,680 EVENTS, AND PROVIDE A PREDICTION 2481 01:36:40,680 --> 01:36:49,000 OF THAT ENDPOINT, SKIN SENSE 2482 01:36:49,000 --> 01:36:49,960 ADVERTIS -- SENSITIZATION, GOOD 2483 01:36:49,960 --> 01:36:51,640 OR BETTER, WE KNOW DEFINED 2484 01:36:51,640 --> 01:36:53,480 APPROACHES BASED ON HUMAN 2485 01:36:53,480 --> 01:36:55,920 BIOLOGY ARE SUPERIOR TO THE 2486 01:36:55,920 --> 01:37:00,720 ANIMAL TEST, AND SO AS A 2487 01:37:00,720 --> 01:37:02,200 FOLLOW-UP TO THAT DASS GUIDELINE 2488 01:37:02,200 --> 01:37:04,440 UNDER OECD WANTED TO MAKE THE 2489 01:37:04,440 --> 01:37:06,640 APPLICATION OF THOSE DEFINED 2490 01:37:06,640 --> 01:37:08,920 APPROACHES MUCH MORE ACCESSIBLE 2491 01:37:08,920 --> 01:37:11,320 ACROSS THE USER COMMUNITY, SO 2492 01:37:11,320 --> 01:37:13,320 KIM FROM THE NICEATM GROUP LED 2493 01:37:13,320 --> 01:37:16,120 DEVELOPMENT OF A USER FRIENDLY 2494 01:37:16,120 --> 01:37:17,440 DASS APP, YOU CAN ACCESS ONLINE 2495 01:37:17,440 --> 01:37:20,320 THROUGH THAT WEB LINK OR BY 2496 01:37:20,320 --> 01:37:23,240 SCANNING THE QR CODE, AND ALLOWS 2497 01:37:23,240 --> 01:37:26,160 USERS TO DOWNLOAD A TEMPLATE AND 2498 01:37:26,160 --> 01:37:28,920 SPREADSHEET THEY CAN UPLOAD 2499 01:37:28,920 --> 01:37:31,800 THEIR OWN DATA IN AND WITH A 2500 01:37:31,800 --> 01:37:36,280 CLICK APPLY DIFFERENT DEFINED 2501 01:37:36,280 --> 01:37:38,040 APPROACHES TO PREDICT HAZARDS OR 2502 01:37:38,040 --> 01:37:41,200 POTENCY CATEGORIES AND HELPS TO 2503 01:37:41,200 --> 01:37:42,720 AVOID ANY OPERATOR ERROR AND 2504 01:37:42,720 --> 01:37:44,280 CONSISTENCY OF APPROACHES AND 2505 01:37:44,280 --> 01:37:46,480 APPLYING DEFINED APPROACHES. 2506 01:37:46,480 --> 01:37:50,160 WE ALSO HAVE A COLLABORATION 2507 01:37:50,160 --> 01:37:51,480 WITH UNILEVER TO DEVELOP, 2508 01:37:51,480 --> 01:37:53,120 FURTHER DEVELOP AND APPLY A 2509 01:37:53,120 --> 01:37:54,640 DEFINED APPROACH FOR SKIN 2510 01:37:54,640 --> 01:37:59,040 ALLERGY RISK ASSESSMENT, THIS IS 2511 01:37:59,040 --> 01:38:01,360 SOMETHING THAT GOES BEYOND 2512 01:38:01,360 --> 01:38:03,280 HAZARD AND POTENCY AND PROVIDES 2513 01:38:03,280 --> 01:38:04,960 A QUANTITATIVE POINT OF 2514 01:38:04,960 --> 01:38:07,240 DEPARTURE TO USE IN RISK 2515 01:38:07,240 --> 01:38:08,760 DEVELOPMENT APPLICATION, IT'S A 2516 01:38:08,760 --> 01:38:11,960 BAYESIAN MODEL WHICH MEANS IT 2517 01:38:11,960 --> 01:38:19,840 ACCOUNTS FOR VARIABILITY AND 2518 01:38:19,840 --> 01:38:20,640 PROVIDES PROBLEMISTIC OUTPUT 2519 01:38:20,640 --> 01:38:21,920 INCLUDING UNCERTAINTY, IF THERE 2520 01:38:21,920 --> 01:38:23,680 ARE EXISTING ANIMAL DATA OR 2521 01:38:23,680 --> 01:38:25,440 EXISTING HUMAN DATA THAT CAN BE 2522 01:38:25,440 --> 01:38:27,320 COMBINED WITH IN VITRO DATA OR 2523 01:38:27,320 --> 01:38:29,360 YOU CAN USE IN VITRO DATA ALONE 2524 01:38:29,360 --> 01:38:30,560 AND DEPENDING ON NUMBER OF 2525 01:38:30,560 --> 01:38:33,280 INPUTS YOU PUT INTO THE MODEL 2526 01:38:33,280 --> 01:38:34,480 YOU'LL GET VARYING 2527 01:38:34,480 --> 01:38:35,920 QUANTIFICATION OF UNCERTAINTY 2528 01:38:35,920 --> 01:38:36,800 AROUND THE OUTPUTS. 2529 01:38:36,800 --> 01:38:41,920 AND OUTPUT OF THE MODEL IS HUMAN 2530 01:38:41,920 --> 01:38:43,360 RELEVANT METRIC OF SENSITIZER 2531 01:38:43,360 --> 01:38:45,000 POTENCY DEFINED AS THE DOSE THAT 2532 01:38:45,000 --> 01:38:48,480 HAS A 1% CHANCE OF SENSITIZATION 2533 01:38:48,480 --> 01:38:52,360 ACROSS A POPULATION, TERMED THE 2534 01:38:52,360 --> 01:38:54,840 ED01, IT'S BEEN ACCEPTED ON THE 2535 01:38:54,840 --> 01:38:57,360 OECD WORK PLAN FOR EVALUATION 2536 01:38:57,360 --> 01:39:01,560 FOR INCLUSION IN DEFINED 2537 01:39:01,560 --> 01:39:02,880 APPROACH GUIDELINE, TG 497, WORK 2538 01:39:02,880 --> 01:39:07,360 ACTIVELY ONGONNA -- ONGOING. 2539 01:39:07,360 --> 01:39:10,840 MANY OF THE PROJECTS THAT I'VE 2540 01:39:10,840 --> 01:39:12,960 TALKED ABOUT ALREADY RELY VERY, 2541 01:39:12,960 --> 01:39:15,880 VERY HEAVILY ON HAVING ROBUST 2542 01:39:15,880 --> 01:39:18,040 REFERENCE DATASETS, AND MOST OF 2543 01:39:18,040 --> 01:39:21,040 THAT REFERENCE DATA CURATION IS 2544 01:39:21,040 --> 01:39:23,000 STILL DONE MANUALLY. 2545 01:39:23,000 --> 01:39:24,520 FROM IDENTIFICATION OF RELEVANT 2546 01:39:24,520 --> 01:39:27,920 PAPERS IN LITERATURE OR 2547 01:39:27,920 --> 01:39:29,000 SUBMISSIONS TO REGULATORY 2548 01:39:29,000 --> 01:39:33,240 AGENCIES, TO EXTRACTING ALL OF 2549 01:39:33,240 --> 01:39:41,000 THAT INFORMATION, TO Q.C.-ING 2550 01:39:41,000 --> 01:39:41,960 EXTRACTION, TO HARMONIZE 2551 01:39:41,960 --> 01:39:44,160 TERMINOLOGIES TO BE COMBINED 2552 01:39:44,160 --> 01:39:46,880 WITH OTHER EXTRACTED 2553 01:39:46,880 --> 01:39:48,000 INFORMATION, INTO LARGE FAIR 2554 01:39:48,000 --> 01:39:51,160 DATASETS, AND WE'RE LOOKING AT 2555 01:39:51,160 --> 01:39:53,120 APPLYING AUGMENTED INTELLIGENCE 2556 01:39:53,120 --> 01:39:54,240 APPROACHES SO USING 2557 01:39:54,240 --> 01:39:57,040 COMPUTATIONAL RESOURCES, LIKE 2558 01:39:57,040 --> 01:39:57,920 NATURAL LANGUAGE PROCESSING, 2559 01:39:57,920 --> 01:40:00,240 ARTIFICIAL INTELLIGENCE, DEEP 2560 01:40:00,240 --> 01:40:01,120 IMAGE PROCESSING, TO ACTUALLY 2561 01:40:01,120 --> 01:40:04,520 AUTOMATE EVERY STEP OF THAT 2562 01:40:04,520 --> 01:40:06,120 PROCESS, SO AUTOMATING 2563 01:40:06,120 --> 01:40:08,240 IDENTIFICATION OF PAPERS THAT 2564 01:40:08,240 --> 01:40:08,760 FULFILL CERTAIN MINIMUM 2565 01:40:08,760 --> 01:40:10,200 CRITERIA, IN TERMS OF THEIR 2566 01:40:10,200 --> 01:40:12,400 STUDY PROTOCOLS TO BE CONSIDERED 2567 01:40:12,400 --> 01:40:13,800 HIGH QUALITY GUIDELINE-LIKE 2568 01:40:13,800 --> 01:40:16,000 PAPERS THAT REGULATORY AGENCIES 2569 01:40:16,000 --> 01:40:17,400 WOULD CONSIDER TO AUTOMATING 2570 01:40:17,400 --> 01:40:18,320 EXTRACTION OF INFORMATION, NOT 2571 01:40:18,320 --> 01:40:20,160 JUST FROM THE TEXT OF THE PAPERS 2572 01:40:20,160 --> 01:40:23,880 BUT ALSO FROM TABLES AND 2573 01:40:23,880 --> 01:40:25,040 FIGURES, TO PROGRAMMATICALLY 2574 01:40:25,040 --> 01:40:26,960 AUTOMATING ANNOTATION OF THAT 2575 01:40:26,960 --> 01:40:29,280 EXTRACTED INFORMATION AND 2576 01:40:29,280 --> 01:40:29,840 APPLYING THOSE STANDARDIZED 2577 01:40:29,840 --> 01:40:31,360 TERMINOLOGYING SO THEY CAN BE 2578 01:40:31,360 --> 01:40:32,800 COMBINED WITH OTHER DATASETS 2579 01:40:32,800 --> 01:40:37,080 THAT ARE ALSO USING CONTROLLED 2580 01:40:37,080 --> 01:40:38,560 VOCABULARIES OR STANDARDIZED 2581 01:40:38,560 --> 01:40:39,680 TERMINOLOGIES. 2582 01:40:39,680 --> 01:40:41,640 THE LAST PIECE, ANNOTATION 2583 01:40:41,640 --> 01:40:42,560 PIECE, WE'RE MAKING GREAT 2584 01:40:42,560 --> 01:40:44,920 PROGRESS BUT THAT PIECE IS 2585 01:40:44,920 --> 01:40:45,280 FURTHEST ALONG. 2586 01:40:45,280 --> 01:40:49,520 WE HAVE A PAPER UNDER REVIEW AT 2587 01:40:49,520 --> 01:40:51,600 EHP RIGHT NOW DEMONSTRATES THE 2588 01:40:51,600 --> 01:40:53,560 APPLICATION OF SOFTWARE TO 2589 01:40:53,560 --> 01:40:54,800 AUTOMATE ANNOTATION PORTION, TO 2590 01:40:54,800 --> 01:40:58,240 A SET OF DEVELOPMENTAL TOXICITY 2591 01:40:58,240 --> 01:40:59,040 GUIDELINE STUDIES. 2592 01:40:59,040 --> 01:41:02,080 ONE THING THAT WAS HIGHLIGHTED 2593 01:41:02,080 --> 01:41:03,720 DURING THE PUBLIC COMMENTING 2594 01:41:03,720 --> 01:41:08,560 PIECE IS IMPORTANCE OF COMMUNITY 2595 01:41:08,560 --> 01:41:10,960 ENGAGEMENT AND OF THE 2596 01:41:10,960 --> 01:41:12,400 OPPORTUNITIES TORE NEW APPROACH 2597 01:41:12,400 --> 01:41:15,160 METHODOLOGIES TO ADDRESS REALLY 2598 01:41:15,160 --> 01:41:17,680 CRITICAL CONSIDERATIONS OF 2599 01:41:17,680 --> 01:41:20,200 HETEROGENEOUS RESPONSES ACROSS 2600 01:41:20,200 --> 01:41:20,480 POPULATIONS. 2601 01:41:20,480 --> 01:41:23,880 UNDERSTANDING THAT NOT ONLY ARE 2602 01:41:23,880 --> 01:41:24,760 HUMANS NOT 200-POUND RATS, WE'RE 2603 01:41:24,760 --> 01:41:26,280 ALSO NOT THE SAME AS ONE 2604 01:41:26,280 --> 01:41:27,840 ANOTHER, RIGHT? 2605 01:41:27,840 --> 01:41:33,880 THERE'S QUITE A DIVERSITY OF 2606 01:41:33,880 --> 01:41:34,960 RESPONSES, AND THERE'S 2607 01:41:34,960 --> 01:41:36,280 SUSCEPTIBILITY FACTORS THAT COME 2608 01:41:36,280 --> 01:41:44,160 INTO PLAY DRIVEN BY GENETICS, 2609 01:41:44,160 --> 01:41:44,720 EPIGENETICS, COMORBIDITIES, 2610 01:41:44,720 --> 01:41:45,320 CO-EXPOSURES, ENVIRONMENTAL 2611 01:41:45,320 --> 01:41:45,680 JUSTICE ISSUES. 2612 01:41:45,680 --> 01:41:47,360 IN OCTOBER LAST YEAR WE 2613 01:41:47,360 --> 01:41:48,960 ORGANIZED THE FIRST WORKSHOP OF 2614 01:41:48,960 --> 01:41:53,040 WHAT WE HOPE WILL BE MANY IN A 2615 01:41:53,040 --> 01:41:55,240 SERIES ON OPPORTUNITIES TO USE 2616 01:41:55,240 --> 01:41:58,840 NEW APPROACH METHODOLOGIES TO 2617 01:41:58,840 --> 01:42:00,320 ADDRESS VARIABILITY AND 2618 01:42:00,320 --> 01:42:02,880 SUSCEPTIBILITY, DIVIDED INTO A 2619 01:42:02,880 --> 01:42:03,440 COUPLE SESSIONS. 2620 01:42:03,440 --> 01:42:04,760 IT WAS LOOKING AT STATE OF THE 2621 01:42:04,760 --> 01:42:06,720 SCIENCE, WHERE DO WE HAVE NAMs 2622 01:42:06,720 --> 01:42:09,040 THAT ARE CAPABLE OF REPRESENTING 2623 01:42:09,040 --> 01:42:11,080 THINGS LIKE GENETIC DIVERSITY 2624 01:42:11,080 --> 01:42:11,880 ACROSS POPULATIONS OR 2625 01:42:11,880 --> 01:42:15,600 REPRESENTING DISEASE STATES THAT 2626 01:42:15,600 --> 01:42:17,440 COULD CONFER VULNERABILITY ON 2627 01:42:17,440 --> 01:42:18,520 INSENSITIVE POPULATIONS, ALSO 2628 01:42:18,520 --> 01:42:20,160 LISTENING AND UNDERSTANDING FROM 2629 01:42:20,160 --> 01:42:22,240 THE COMMUNITY WHAT ARE THE 2630 01:42:22,240 --> 01:42:25,080 CONCERNS THAT THEY HAVE WHEN IT 2631 01:42:25,080 --> 01:42:28,200 COMES TO THEIR EXPERIENCE AND 2632 01:42:28,200 --> 01:42:31,000 ENVIRONMENTAL EXPOSURES AND 2633 01:42:31,000 --> 01:42:32,320 SENSITIVE AND SUSCEPTIBLE 2634 01:42:32,320 --> 01:42:34,000 SUBPOPULATIONS, THAT WORKSHOP 2635 01:42:34,000 --> 01:42:36,040 WAS CO-LED BY THE NIEHS DEPUTY 2636 01:42:36,040 --> 01:42:37,480 DIRECTOR AROUND ALISON HARRILL 2637 01:42:37,480 --> 01:42:41,200 OUR COLLEAGUE FROM THE U.S. EPA. 2638 01:42:41,200 --> 01:42:44,160 ONE AREA WE'RE TRYING TO 2639 01:42:44,160 --> 01:42:45,360 INCORPORATE VARIABILITY IN 2640 01:42:45,360 --> 01:42:49,000 POPULATIONS IN OUR TOOLS IN ICE 2641 01:42:49,000 --> 01:42:53,360 IN PARTICULAR IS THROUGH MA 2642 01:42:53,360 --> 01:42:53,800 METABOLISM. 2643 01:42:53,800 --> 01:42:55,760 WE HAVE SOME LEVEL INCORPORATED 2644 01:42:55,760 --> 01:43:00,040 BUT IT'S ONLY INTEGRATED VIA 2645 01:43:00,040 --> 01:43:03,200 VIRTUAL POPULATION SIMULATIONS, 2646 01:43:03,200 --> 01:43:06,160 GENERIC PBPK MODELS, 2647 01:43:06,160 --> 01:43:07,240 DISTRIBUTION OF PARAMETERS, AGE, 2648 01:43:07,240 --> 01:43:08,600 WEIGHT, CARDIAC OUTPUT, ET 2649 01:43:08,600 --> 01:43:11,000 CETERA, ALLOWS US TO AT LEAST 2650 01:43:11,000 --> 01:43:13,400 ESTIMATE SOME CONFIDENCE 2651 01:43:13,400 --> 01:43:15,040 INTERVALS AROUND INTERNAL 2652 01:43:15,040 --> 01:43:15,680 CONCENTRATIONS. 2653 01:43:15,680 --> 01:43:18,520 BUT WE KNOW THAT GENETIC 2654 01:43:18,520 --> 01:43:20,720 POLYMORPHISMS IN THE POPULATION 2655 01:43:20,720 --> 01:43:22,800 IN METABOLIC ENZYMES CAN REALLY 2656 01:43:22,800 --> 01:43:26,520 EXPERT STRONG INFLUENCES ON 2657 01:43:26,520 --> 01:43:28,600 PEOPLE'S ABILITY TO METABOLIZE 2658 01:43:28,600 --> 01:43:30,240 ANTIBIOTICS AND POTENTIALLY HAVE 2659 01:43:30,240 --> 01:43:34,600 HOW THEY MAY REACT TO XENOBIOTIC 2660 01:43:34,600 --> 01:43:37,600 EXPOSURE, PARTNERING WITH THE 2661 01:43:37,600 --> 01:43:41,280 EUROPEAN FOOD SAFE AGENCY 2662 01:43:41,280 --> 01:43:42,360 LOOKING AT ENZYMATIC ACTIVITIES 2663 01:43:42,360 --> 01:43:45,760 IN VITRO AND IN VIVO AND LOOK AT 2664 01:43:45,760 --> 01:43:48,440 ALLELIC FREQUENCY OF SINGLE 2665 01:43:48,440 --> 01:43:49,520 NUCLEOTIDE POLYMORPHISMS IN 2666 01:43:49,520 --> 01:43:51,480 METABOLIC ENZYMES SO WE'RE 2667 01:43:51,480 --> 01:43:53,000 INCORPORATING ALL OF THAT 2668 01:43:53,000 --> 01:43:54,000 INFORMATION INTO OUR 2669 01:43:54,000 --> 01:43:54,560 COMPUTATIONAL MODELS. 2670 01:43:54,560 --> 01:43:57,520 SO THIS IS OUR WORK FLOW FOR 2671 01:43:57,520 --> 01:43:58,120 THAT. 2672 01:43:58,120 --> 01:44:00,240 BASICALLY THE WORK FLOW PROVIDES 2673 01:44:00,240 --> 01:44:03,080 TISSUE LEVEL CONCENTRATIONS OF 2674 01:44:03,080 --> 01:44:04,280 METABOLITES WITH CONFIDENCE 2675 01:44:04,280 --> 01:44:06,560 INTERVALS DERIVED FROM THE 2676 01:44:06,560 --> 01:44:07,480 VARIABILITY AND ENZYME 2677 01:44:07,480 --> 01:44:12,280 EXPRESSION ACROSS THE 2678 01:44:12,280 --> 01:44:13,840 POPULATION. 2679 01:44:13,840 --> 01:44:16,760 THAT'S INCORPORATED INTO PBBK 2680 01:44:16,760 --> 01:44:17,840 MODELS WITH CLEARANCE RATES 2681 01:44:17,840 --> 01:44:19,200 BASED ON COEFFICIENT OF 2682 01:44:19,200 --> 01:44:19,840 VARIATION ACROSS A POPULATION 2683 01:44:19,840 --> 01:44:24,960 AND SO FOR WE'VE DONE THIS FOR 2684 01:44:24,960 --> 01:44:27,600 CYP 3A4 AND 2D 6 TRYING TO MOVE 2685 01:44:27,600 --> 01:44:28,920 INTO OTHER COMMONLY EXPRESSED 2686 01:44:28,920 --> 01:44:29,920 CYP ENZYMES. 2687 01:44:29,920 --> 01:44:31,120 I'M EXCITED ABOUT THIS ABILITY 2688 01:44:31,120 --> 01:44:33,960 TO LOOK NOT ONLY AT THE 2689 01:44:33,960 --> 01:44:35,160 CONCENTRATION OF PARENT 2690 01:44:35,160 --> 01:44:38,000 CHEMICALS BUT ALSO PREDICTED 2691 01:44:38,000 --> 01:44:38,880 CONCENTRATION OF METABOLITE 2692 01:44:38,880 --> 01:44:41,280 CHEMICALS AND HAVE CONFIDENCE 2693 01:44:41,280 --> 01:44:42,400 INTERVAL THAT REPRESENTS THAT 2694 01:44:42,400 --> 01:44:44,440 POPULATION RANGE AND WE CAN FEED 2695 01:44:44,440 --> 01:44:47,840 THOSE INTO OUR TOXICITY 2696 01:44:47,840 --> 01:44:58,120 PREDICTION MODELS AND GET BETTER 2697 01:44:58,120 --> 01:44:59,400 REPRESENTATION OF SUSCEPTIBILITY 2698 01:44:59,400 --> 01:45:00,320 ACROSS A POPULATION. 2699 01:45:00,320 --> 01:45:03,080 ANOTHER IS TRY AND EXTEND 2700 01:45:03,080 --> 01:45:07,440 UTILITY OF THE IN VITRO 2701 01:45:07,440 --> 01:45:08,120 HIGH-THROUGHPUT SCREENING DATA 2702 01:45:08,120 --> 01:45:09,640 FROM TOX21 SAND INCORPORATE 2703 01:45:09,640 --> 01:45:12,160 EXPOSURE INFORMATION FROM FROM 2704 01:45:12,160 --> 01:45:14,360 DATABASES TO PREDICT THE 2705 01:45:14,360 --> 01:45:16,000 GEOSPATIAL RISK ACROSS 2706 01:45:16,000 --> 01:45:16,840 POPULATIONS AND ACROSS 2707 01:45:16,840 --> 01:45:17,400 COMMUNITIES. 2708 01:45:17,400 --> 01:45:18,480 AND SO WHAT WE'VE DONE HERE, 2709 01:45:18,480 --> 01:45:20,440 THIS IS A PROOF OF CONCEPT WHERE 2710 01:45:20,440 --> 01:45:23,520 WE LOOKED AT 41 CHEMICALS, THAT 2711 01:45:23,520 --> 01:45:27,400 ARE KNOWN AIR TOXIC, FROM THE 2712 01:45:27,400 --> 01:45:30,040 NATIONAL AIR TOXICS ASSESSMENT 2713 01:45:30,040 --> 01:45:32,080 DATABASE, AND THESE COMPOUNDS 2714 01:45:32,080 --> 01:45:34,160 HAVE A COMMON MOLECULAR TARGET, 2715 01:45:34,160 --> 01:45:38,680 SO THEY HAVE ALL PERTURBED 2716 01:45:38,680 --> 01:45:39,680 HIGH-THROUGHPUT SCREENING ASSAY 2717 01:45:39,680 --> 01:45:44,040 FOR UPREGULATION WHICH IS A 2718 01:45:44,040 --> 01:45:45,800 TARGET INVOLVED IN DISEASE 2719 01:45:45,800 --> 01:45:46,920 ETIOLOGY INCLUDING METABOLIC 2720 01:45:46,920 --> 01:45:47,560 DISRUPTION. 2721 01:45:47,560 --> 01:45:49,640 WE FIRST APPLIED IN VITRO AND IN 2722 01:45:49,640 --> 01:45:52,600 VIVO EXTRAPOLATION TO ESTIMATE 2723 01:45:52,600 --> 01:45:55,360 INTERNAL EXPOSURES BY CONVERTING 2724 01:45:55,360 --> 01:46:01,280 INHALED CONCENTRATION TO PLASMA 2725 01:46:01,280 --> 01:46:02,560 CONCENTRATION USING PBBK MODELS 2726 01:46:02,560 --> 01:46:04,520 CAN COUNTY SPECIFIC INFORMATION 2727 01:46:04,520 --> 01:46:08,040 AND USED THAT ESTIMATED PLASMA 2728 01:46:08,040 --> 01:46:08,720 CONCENTRATION AND CONCENTRATION 2729 01:46:08,720 --> 01:46:10,800 RESPONSE CURVES FROM IN VITRO 2730 01:46:10,800 --> 01:46:12,440 HIGH-THROUGHPUT SCREENING ASSAYS 2731 01:46:12,440 --> 01:46:13,040 TO DETERMINE CHEMICAL-SPECIFIC 2732 01:46:13,040 --> 01:46:15,160 EFFECTS IN EACH OF THE MIXTURE 2733 01:46:15,160 --> 01:46:18,000 COMPONENTS AND COMBINE THOSE 2734 01:46:18,000 --> 01:46:19,280 USING THREE MIXTURE MODELING 2735 01:46:19,280 --> 01:46:21,200 METHODS TO ESTIMATE THE JOINT 2736 01:46:21,200 --> 01:46:23,480 EFFECT FROM EXPOSURES TO THOSE 2737 01:46:23,480 --> 01:46:24,360 CHEMICAL MIXTURES ON THE 2738 01:46:24,360 --> 01:46:27,640 ACTIVITY LEVELS WHICH ARE THEN 2739 01:46:27,640 --> 01:46:29,240 GEOSPATIALLY MAPPED ACROSS THE 2740 01:46:29,240 --> 01:46:29,640 UNITED STATES. 2741 01:46:29,640 --> 01:46:32,040 AND SO THIS IS REALLY A PROOF OF 2742 01:46:32,040 --> 01:46:35,680 CONCEPT WORK FLOW THAT CAN CHEM 2743 01:46:35,680 --> 01:46:38,520 STRAIGHT USING NAMs LIKE 2744 01:46:38,520 --> 01:46:42,080 HIGH-THROUGHPUT DATA TO PREDICT 2745 01:46:42,080 --> 01:46:44,760 EARLY PERTURBATIONINGS AND MAP 2746 01:46:44,760 --> 01:46:45,760 THAT GEOSPATIALLY, THE NEXT STEP 2747 01:46:45,760 --> 01:46:51,000 WOULD BE TO CONNECT TO ADVERSITY 2748 01:46:51,000 --> 01:46:52,160 FROM ELECTRONIC HEALTH RECORDS. 2749 01:46:52,160 --> 01:46:53,320 ANOTHER PROJECT OFF THE GROUND 2750 01:46:53,320 --> 01:46:57,440 IN THE LAST SIX MONTHS IS 2751 01:46:57,440 --> 01:46:58,720 SUPPORTING METHOD DEVELOPED BY 2752 01:46:58,720 --> 01:47:00,960 OUR COLLEAGUES AT THE U.S. EPA 2753 01:47:00,960 --> 01:47:01,960 OFFICE OF RESEARCH AND 2754 01:47:01,960 --> 01:47:04,360 DEVELOPMENT, CHAD IS THE LEAD 2755 01:47:04,360 --> 01:47:06,640 HERE FROM RUSTY THOMAS' GROUP, 2756 01:47:06,640 --> 01:47:09,840 DEVELOPED A 3D HUMAN THYROID 2757 01:47:09,840 --> 01:47:11,880 MICROTISSUE ASSAY, SO CONSISTING 2758 01:47:11,880 --> 01:47:15,840 OF PRIMARY HUMAN THYROID CELLS 2759 01:47:15,840 --> 01:47:18,400 AND ASSESSING THYROID HORMONE 2760 01:47:18,400 --> 01:47:23,080 INHIBITION, IN A 96 WELL FORMAT, 2761 01:47:23,080 --> 01:47:25,160 HAS SHOWN PROMISING DATA IN 2762 01:47:25,160 --> 01:47:28,280 RESPONSE TO REFERENCE CHEMICALS, 2763 01:47:28,280 --> 01:47:29,560 SO WE'RE COORDINATING 2764 01:47:29,560 --> 01:47:30,240 INTERLABORATORY PRE-VALIDATION 2765 01:47:30,240 --> 01:47:32,520 STUDY, THERE'S A NUMBER OF LABS 2766 01:47:32,520 --> 01:47:36,240 THAT ARE ENGAGED HERE, LIFE NET 2767 01:47:36,240 --> 01:47:42,040 HEALTH, BAYER CROPSCIENCE, 2768 01:47:42,040 --> 01:47:42,920 CORTEVA, RECRUITED DOMESTIC AND 2769 01:47:42,920 --> 01:47:44,080 INTERNATIONAL REPRESENTATIVES TO 2770 01:47:44,080 --> 01:47:46,400 OUR VALIDATION MANAGEMENT TEAM, 2771 01:47:46,400 --> 01:47:47,640 REVIEWED THE SOP PROVIDED A 2772 01:47:47,640 --> 01:47:49,720 NUMBER OF POINTS OF FEEDBACK 2773 01:47:49,720 --> 01:47:51,240 THAT HAVE BEEN INCORPORATED, AND 2774 01:47:51,240 --> 01:47:56,160 SO NOW WE HAVE THE MATERIALS, 2775 01:47:56,160 --> 01:47:58,000 AGREEMENTS, MCRADA IN PLACE TO 2776 01:47:58,000 --> 01:47:59,640 DO TRANSFERABILITY TO LABS, VERY 2777 01:47:59,640 --> 01:48:00,720 EXCITED ABOUT THIS PROJECT. 2778 01:48:00,720 --> 01:48:04,160 AND WITH THE EVENTUAL GOAL OF 2779 01:48:04,160 --> 01:48:06,000 SOMEDAY TAKING THIS TO OECD AS 2780 01:48:06,000 --> 01:48:09,400 POTENTIAL TEST GUIDELINE. 2781 01:48:09,400 --> 01:48:14,240 MOST OF YOU HEARD ME TALK ABOUT 2782 01:48:14,240 --> 01:48:15,000 THE MPSCoRE WORK GROUP, 2783 01:48:15,000 --> 01:48:18,120 STARTED AT THE BEGINNING OF THE 2784 01:48:18,120 --> 01:48:23,160 PANDEMIC IN RESPONSE TO QUICKLY 2785 01:48:23,160 --> 01:48:24,720 EMERGING EVIDENCE ANIMAL MODELS 2786 01:48:24,720 --> 01:48:27,920 WERE NOT GOOD SURROGATES FOR 2787 01:48:27,920 --> 01:48:28,680 UNDERSTANDING PATHOPHYSIOLOGY OF 2788 01:48:28,680 --> 01:48:29,840 SARS-COV-2 IN HUMANS AND 2789 01:48:29,840 --> 01:48:32,240 POTENTIALLY NOT VERY GOOD 2790 01:48:32,240 --> 01:48:33,480 TESTING PLATFORMS FOR 2791 01:48:33,480 --> 01:48:36,760 UNDERSTANDING UTILITY OF 2792 01:48:36,760 --> 01:48:37,440 THERAPEUTICS. 2793 01:48:37,440 --> 01:48:40,160 SO THIS WAS GRAVE HUMAN HEALTH, 2794 01:48:40,160 --> 01:48:42,640 PUBLIC HEALTH CRISIS BUT ALSO 2795 01:48:42,640 --> 01:48:44,480 REALLY STRONG OPPORTUNITY FOR 2796 01:48:44,480 --> 01:48:47,400 NEW APPROACH METHODS IN 2797 01:48:47,400 --> 01:48:48,720 PARTICULAR MICROPHYSIOLOGIC 2798 01:48:48,720 --> 01:48:50,560 SYSTEMS REPRESENTING COMPLEXITY 2799 01:48:50,560 --> 01:48:53,880 OF HUMAN BIOLOGY TO PROVIDE 2800 01:48:53,880 --> 01:48:55,200 INFORMATION ON PATHOPHYSIOLOGY, 2801 01:48:55,200 --> 01:48:56,840 DISEASE MECHANISMS, AND 2802 01:48:56,840 --> 01:48:58,360 PLATFORMS TO TEST NOVEL 2803 01:48:58,360 --> 01:48:58,840 THERAPEUTICS. 2804 01:48:58,840 --> 01:49:02,840 SO WE FORMED THIS GLOBAL WORKING 2805 01:49:02,840 --> 01:49:04,400 GROUP, MPSCoRE, CO-LED BY 2806 01:49:04,400 --> 01:49:12,880 PARTNERS IN THE U.K., NC3Rs, 2807 01:49:12,880 --> 01:49:14,520 FUNDING PROJECTS UNDER THIS 2808 01:49:14,520 --> 01:49:15,000 MPSCoRE CORE INCLUDING 2809 01:49:15,000 --> 01:49:18,680 DEVELOPMENT OF A PORTAL IN THE 2810 01:49:18,680 --> 01:49:21,440 DATABASE, NOW BIOSTATISTICS 2811 01:49:21,440 --> 01:49:24,400 PLATFORM FUNDED BY NCATS UNDER 2812 01:49:24,400 --> 01:49:27,480 TISSUE CHIPS GRANT PROGRAM. 2813 01:49:27,480 --> 01:49:36,080 WE'RE NOW EXTENDING, CO-IS CO-E 2814 01:49:36,080 --> 01:49:40,000 TRANSITIONING TO LOOK AT MORE 2815 01:49:40,000 --> 01:49:41,560 BROAD APPLICABILITY OF THESE 2816 01:49:41,560 --> 01:49:43,400 MODELS NOT JUST TO COVID BUT 2817 01:49:43,400 --> 01:49:44,360 OTHER INFECTIOUS DISEASES. 2818 01:49:44,360 --> 01:49:47,440 SO AT THE END OF THIS MONTH, MAY 2819 01:49:47,440 --> 01:49:50,520 31 AND JUNE 1, WE HAVE TWO HALF 2820 01:49:50,520 --> 01:49:55,000 DAYS IN THE MORNING, SYMPOSIUM 2821 01:49:55,000 --> 01:49:56,840 ON ADVANCING RESEARCH AND 2822 01:49:56,840 --> 01:49:57,880 REGULATORY ACCEPTANCE FOR 2823 01:49:57,880 --> 01:49:58,960 INFECTIOUS DISEASE APPLICATIONS 2824 01:49:58,960 --> 01:50:01,200 AND WE HAVE A REALLY EXCITING 2825 01:50:01,200 --> 01:50:05,120 AGENDA, UP ON THE WEBSITE, WE'VE 2826 01:50:05,120 --> 01:50:07,160 GOT PARTICIPANTS FROM FDA, FROM 2827 01:50:07,160 --> 01:50:10,560 NIAID, FROM U.S. ARMY, NATIONAL 2828 01:50:10,560 --> 01:50:12,120 BIODEFENSE ANALYSIS AND 2829 01:50:12,120 --> 01:50:13,720 COUNTERMEASURES CENTER, U.K. 2830 01:50:13,720 --> 01:50:18,720 HEALTH SECURITY AGENCY, A NUMBER 2831 01:50:18,720 --> 01:50:20,960 OF ACADEMIC COLLABORATORS FROM 2832 01:50:20,960 --> 01:50:22,480 HARVARD WYSS INSTITUTE, AND ONE 2833 01:50:22,480 --> 01:50:23,760 OF MY PARTNERS IN CRIME DAN 2834 01:50:23,760 --> 01:50:29,920 TAGLE IS IS HERE IN THE ROOM AD 2835 01:50:29,920 --> 01:50:31,240 WE'LL HEAR FROM HIM. 2836 01:50:31,240 --> 01:50:33,080 THE LAST THING I'LL JUST BRING 2837 01:50:33,080 --> 01:50:34,680 TO YOUR AWARENESS IS A WORKSHOP 2838 01:50:34,680 --> 01:50:35,600 WE'RE PLANNING AT THE END OF 2839 01:50:35,600 --> 01:50:38,680 THIS YEAR, IN THE FALL ACTUALLY, 2840 01:50:38,680 --> 01:50:42,720 IN OCTOBER, ON NEW APPROACH 2841 01:50:42,720 --> 01:50:43,280 METHODOLOGIES TO MODEL 2842 01:50:43,280 --> 01:50:45,040 GASTROINTESTINAL TRACT FOR A 2843 01:50:45,040 --> 01:50:48,080 VARIETY OF DIFFERENT PURPOSES. 2844 01:50:48,080 --> 01:50:49,640 SO ONE LOOKING AT DE-RISKING 2845 01:50:49,640 --> 01:50:53,120 CHEMICALS FOR SYSTEMIC TOXICITY, 2846 01:50:53,120 --> 01:50:54,320 UNDERSTANDING IF YOU HAVE ORAL 2847 01:50:54,320 --> 01:50:58,440 EXPOSURE TO CHEMICALS ARE THOSE 2848 01:50:58,440 --> 01:50:59,840 CHEMICALS METABOLIZED, ABSORBED 2849 01:50:59,840 --> 01:51:02,680 THROUGH THE GUT WALL, DO THEY 2850 01:51:02,680 --> 01:51:04,080 JUST GET PASSED THROUGH THE 2851 01:51:04,080 --> 01:51:07,280 BODY, DO THEY CAUSE G.I. 2852 01:51:07,280 --> 01:51:09,320 TOXICITY THROUGH MICROBIOME OR 2853 01:51:09,320 --> 01:51:15,560 OTHERWISE, DO THEY CAUSE 2854 01:51:15,560 --> 01:51:19,400 ALLERGENAGAIN ISTY -- GENICITY, 2855 01:51:19,400 --> 01:51:20,960 IF YOU'RE INTERESTED IN BEING 2856 01:51:20,960 --> 01:51:23,800 INVOLVED AS A SPEAKER OR HAVE 2857 01:51:23,800 --> 01:51:25,080 RECOMMENDATIONS PLEASE REACH 2858 01:51:25,080 --> 01:51:25,240 OUT. 2859 01:51:25,240 --> 01:51:28,560 WE'RE NOT FINALIZED IN TERMS OF 2860 01:51:28,560 --> 01:51:33,560 AGENDA YET BUT THIS WILL BE AN 2861 01:51:33,560 --> 01:51:34,320 IN-PERSON MEETING IN BETHESDA 2862 01:51:34,320 --> 01:51:36,640 WITH A SERIES OF WEBINARS TO SET 2863 01:51:36,640 --> 01:51:38,320 THE SCENE FOR THIS TOPIC. 2864 01:51:38,320 --> 01:51:40,880 THANK YOU SO MUCH FOR YOUR 2865 01:51:40,880 --> 01:51:41,440 ATTENTION. 2866 01:51:41,440 --> 01:51:44,480 I SHOWED YOU THE BIG PICTURE OF 2867 01:51:44,480 --> 01:51:46,440 THE DTT FOLKS HALFWAY THROUGH 2868 01:51:46,440 --> 01:51:47,640 THE PRESENTATION, I DIDN'T HAVE 2869 01:51:47,640 --> 01:51:49,280 ROOM TO FIT THEM ON THE SLIDE 2870 01:51:49,280 --> 01:51:52,360 BUT THIS IS THE NICEATM GROUP 2871 01:51:52,360 --> 01:51:53,680 THAT I HAVE THE INCREDIBLE 2872 01:51:53,680 --> 01:51:56,280 PRIVILEGE OF WORKING WITH EVERY 2873 01:51:56,280 --> 01:52:00,640 DAY, IN PARTICULAR OUR 2874 01:52:00,640 --> 01:52:01,640 CONTRACTORS PROVIDE ABSOLUTELY 2875 01:52:01,640 --> 01:52:03,640 AMAZING SUPPORT FROM A 2876 01:52:03,640 --> 01:52:04,240 SCIENTIFIC AND OPERATIONAL 2877 01:52:04,240 --> 01:52:06,040 PERSPECTIVE AND NONE OF THE WORK 2878 01:52:06,040 --> 01:52:08,040 THAT NICEATM DOES IN SUPPORT OF 2879 01:52:08,040 --> 01:52:10,960 ICCVAM WOULD BE POSSIBLE WITHOUT 2880 01:52:10,960 --> 01:52:12,080 THIS WONDERFUL GROUP OF PEOPLE. 2881 01:52:12,080 --> 01:52:14,040 THANKS VERY MUCH AND I'LL TAKE 2882 01:52:14,040 --> 01:52:14,480 ANY QUESTIONS. 2883 01:52:14,480 --> 01:52:16,880 [APPLAUSE] 2884 01:52:16,880 --> 01:52:24,120 2885 01:52:24,120 --> 01:52:27,280 >> SO, THE HUMAN GUT MODEL, 2886 01:52:27,280 --> 01:52:28,800 THAT WILL INCORPORATE THE 2887 01:52:28,800 --> 01:52:32,400 MICROBIOME AS WELL? 2888 01:52:32,400 --> 01:52:33,840 >>THAT'S A FOCAL AREA WE 2889 01:52:33,840 --> 01:52:34,640 IDENTIFIED AS BEING IMPORTANT. 2890 01:52:34,640 --> 01:52:36,600 WE HAVE A NUMBER OF POTENTIAL 2891 01:52:36,600 --> 01:52:39,320 SPEAKERS IDENTIFIED FOR THAT BUT 2892 01:52:39,320 --> 01:52:41,280 WE'RE ALWAYS LOOKING FOR 2893 01:52:41,280 --> 01:52:41,800 ADDITIONAL SUGGESTIONS. 2894 01:52:41,800 --> 01:52:42,720 >> EXCELLENT. 2895 01:52:42,720 --> 01:52:44,240 THANKS. 2896 01:52:44,240 --> 01:52:47,200 2897 01:52:47,200 --> 01:52:47,400 OKAY. 2898 01:52:47,400 --> 01:52:48,520 AND REMEMBER, FOLKS ON THE 2899 01:52:48,520 --> 01:52:51,040 WEBCAST, PLEASE DO SEND YOUR 2900 01:52:51,040 --> 01:52:53,240 QUESTIONS TO THE ICCVAM 2901 01:52:53,240 --> 01:52:53,880 QUESTIONS E-MAIL ADDRESS. 2902 01:52:53,880 --> 01:52:57,720 NOW IT IS MY PLEASURE TO -- 2903 01:52:57,720 --> 01:52:59,560 WE'RE RUNNING BEHIND TIME BUT I 2904 01:52:59,560 --> 01:53:00,560 THINK WE'RE FINE. 2905 01:53:00,560 --> 01:53:03,080 WE'RE GOING TO CONTINUE ON THE 2906 01:53:03,080 --> 01:53:05,400 AGENDA AND DO THE ICCVAM 2907 01:53:05,400 --> 01:53:07,600 WORKGROUP UPDATE THAT DR. ALLEN 2908 01:53:07,600 --> 01:53:09,560 IS GOING TO GIVE, AND THEN WE 2909 01:53:09,560 --> 01:53:10,920 WILL BREAK. 2910 01:53:10,920 --> 01:53:12,440 PROBABLY I'M GUESSING WE'LL 2911 01:53:12,440 --> 01:53:15,480 BREAK AT 11:15 OR 11:20, BUT 2912 01:53:15,480 --> 01:53:17,640 TAKE YOUR TIME, DAVE. 2913 01:53:17,640 --> 01:53:20,160 >> THANKS, NICOLE. 2914 01:53:20,160 --> 01:53:21,680 I'VE ONLY GOT 332 SLIDES. 2915 01:53:21,680 --> 01:53:23,120 SHOULDN'T BE LONG. 2916 01:53:23,120 --> 01:53:27,280 NO, AS NICOLE SAID, I'M DAVE 2917 01:53:27,280 --> 01:53:29,240 ALLEN, PRINCIPAL INVESTIGATOR 2918 01:53:29,240 --> 01:53:31,760 FOR THE CONTRACTOR FOR NICEATM, 2919 01:53:31,760 --> 01:53:32,840 IT'S A PLEASURE TO BE HERE TO 2920 01:53:32,840 --> 01:53:34,600 TALK ABOUT THE GREAT WORK THE 2921 01:53:34,600 --> 01:53:36,040 COMMITTEE HAS BEEN INVOLVED IN 2922 01:53:36,040 --> 01:53:37,360 THROUGH THEIR WORK GROUPS. 2923 01:53:37,360 --> 01:53:40,040 FOLKS HERE, MOST FOLKS ARE AWARE 2924 01:53:40,040 --> 01:53:42,000 OF THIS BUT ICCVAM A COMMITTEE 2925 01:53:42,000 --> 01:53:43,840 OF VOLUNTEERS, FOLKS ON THE 2926 01:53:43,840 --> 01:53:48,200 FORMAL ICCVAM COMMITTEE, THIS IS 2927 01:53:48,200 --> 01:53:49,840 REALLY THEIR OTHER DUTIES IN 2928 01:53:49,840 --> 01:53:51,120 THEIR JOB DESCRIPTION, THEY PUT 2929 01:53:51,120 --> 01:53:52,880 A LOT OF EFFORT INTO WHAT THEY 2930 01:53:52,880 --> 01:53:54,880 ARE DOING BUT THEY NEED EXPERTS 2931 01:53:54,880 --> 01:53:56,600 WITHIN THEIR AGENCIES TO GET 2932 01:53:56,600 --> 01:53:58,800 SOME QUESTIONS ANSWERED OR SOME 2933 01:53:58,800 --> 01:54:00,120 OF THESE DETAILS ADDRESSED, SO 2934 01:54:00,120 --> 01:54:02,080 THEY DO THAT VIA WORK GROUPS. 2935 01:54:02,080 --> 01:54:07,640 MANY OF THE FOLKS PARTICIPATE IN 2936 01:54:07,640 --> 01:54:10,160 THE ICCVAM WORK GROUPS BUT 2937 01:54:10,160 --> 01:54:11,240 CERTAINLY IT'S INCUMBENT ON 2938 01:54:11,240 --> 01:54:15,080 OTHERS IN THE AGENCIES AND 2939 01:54:15,080 --> 01:54:17,240 INSTITUTES TO PROVIDE EXPERTISE 2940 01:54:17,240 --> 01:54:19,040 AND THEN US AT THE NICEATM 2941 01:54:19,040 --> 01:54:20,880 SUPPORT CONTRACT TEAM AS NICOLE 2942 01:54:20,880 --> 01:54:22,720 MENTIONED WE PROVIDE SCIENTIFIC 2943 01:54:22,720 --> 01:54:24,360 AND OPERATIONAL SUPPORT BEHIND 2944 01:54:24,360 --> 01:54:29,200 THE SCENES AND SORT OF THE 2945 01:54:29,200 --> 01:54:30,840 PROVIDE INFORMATION, DETAILED, 2946 01:54:30,840 --> 01:54:32,320 OFFER MODELS AND NEW INFORMATION 2947 01:54:32,320 --> 01:54:34,560 FOR COMMENT FROM THE WORK GROUPS 2948 01:54:34,560 --> 01:54:38,360 TO MOVE FORWARD THAT WAY. 2949 01:54:38,360 --> 01:54:42,000 SO, THERE ARE NOW A TOTAL OF 2950 01:54:42,000 --> 01:54:43,000 SEVEN ACTIVE ICCVAM WORK GROUPS, 2951 01:54:43,000 --> 01:54:45,720 YOU CAN SEE THEM LISTED HERE. 2952 01:54:45,720 --> 01:54:47,680 NEWEST ONE ASSOCIATED WITH PFAS 2953 01:54:47,680 --> 01:54:49,240 TOXICITY, AND WE'LL TALK BRIEFLY 2954 01:54:49,240 --> 01:54:50,440 ABOUT THAT AT THE END BUT 2955 01:54:50,440 --> 01:54:56,680 CERTAINLY A LOT OF EFFORT AND 2956 01:54:56,680 --> 01:54:59,080 THIS IS ALSO -- FRANK BARILE'S 2957 01:54:59,080 --> 01:55:00,840 COMMENTS WERE A NICE SEGUE TO 2958 01:55:00,840 --> 01:55:06,520 THE WORK ICCVAM HAS DONE OVER 2959 01:55:06,520 --> 01:55:09,240 THE PAST FIVE YEARS SINCE IT 2960 01:55:09,240 --> 01:55:10,880 MODERNIZED OR EVOLVED SINCE 2961 01:55:10,880 --> 01:55:11,880 REINVENTING ITSELF AND FOCUSING 2962 01:55:11,880 --> 01:55:15,040 THROUGH A STRATEGIC ROAD MAP 2963 01:55:15,040 --> 01:55:17,600 PUBLISHED IN 2018 ON FOCUSING ON 2964 01:55:17,600 --> 01:55:21,720 END USERS, MATILY -- ULTIMATELY 2965 01:55:21,720 --> 01:55:24,240 WHAT QUESTIONS NEED TO BE ANSWER 2966 01:55:24,240 --> 01:55:26,640 AND MODELS DEVELOPED 2967 01:55:26,640 --> 01:55:26,960 ACCORDINGLY. 2968 01:55:26,960 --> 01:55:30,120 ACUTE TOXICITY, A TREMENDOUS 2969 01:55:30,120 --> 01:55:32,000 AMOUNT OF INVOLVEMENT AND 2970 01:55:32,000 --> 01:55:32,880 PROGRESS OVER THE LAST SEVERAL 2971 01:55:32,880 --> 01:55:34,000 YEARS. 2972 01:55:34,000 --> 01:55:36,600 CERTAINLY IN THE AREA OF ACUTE 2973 01:55:36,600 --> 01:55:38,240 ORAL AND DERMAL SYSTEMIC 2974 01:55:38,240 --> 01:55:39,880 TOXICITY, AND EACH ONE OF THESE 2975 01:55:39,880 --> 01:55:43,800 SLIDES, EACH WORK GROUP WHEN 2976 01:55:43,800 --> 01:55:45,440 IT'S CREATED, IT'S INCUMBENT ON 2977 01:55:45,440 --> 01:55:47,320 ICCVAM AGENCIES TO HAVE A 2978 01:55:47,320 --> 01:55:48,600 SPONSORING -- ONE OR MORE 2979 01:55:48,600 --> 01:55:49,600 SPONSORING AGENCY, THEY HAVE 2980 01:55:49,600 --> 01:55:52,560 QUESTIONS OR PROBLEMS THAT THEY 2981 01:55:52,560 --> 01:55:55,200 ARE TRYING TO ADDRESS, AND THE 2982 01:55:55,200 --> 01:55:57,160 WORK GROUP DEVELOPS A SCOPE AND 2983 01:55:57,160 --> 01:55:59,000 CHARGE THAT THEY THEN 2984 01:55:59,000 --> 01:56:00,720 METHODICALLY WORK THROUGH WITH 2985 01:56:00,720 --> 01:56:02,720 THE SUPPORT OF NICEATM, AND AT 2986 01:56:02,720 --> 01:56:04,320 THE END ULTIMATELY THEY HAVE ALL 2987 01:56:04,320 --> 01:56:07,320 THEIR BOXES CHECKED WITH ALL 2988 01:56:07,320 --> 01:56:09,400 THEIR SCOPE AND CHARGE AND CAN 2989 01:56:09,400 --> 01:56:11,400 SEND TO EXPERT GROUP OR BE 2990 01:56:11,400 --> 01:56:12,480 TASKED WITH ADDITIONAL EFFORT. 2991 01:56:12,480 --> 01:56:13,920 EACH OF THE SLIDES WALK THROUGH 2992 01:56:13,920 --> 01:56:18,360 THAT SCOPE AND CHARGE FORMAT. 2993 01:56:18,360 --> 01:56:22,320 THE INITIAL THING WAS TO FOCUS 2994 01:56:22,320 --> 01:56:25,160 ON UTILITY OF USING LD 50 DATA 2995 01:56:25,160 --> 01:56:26,360 FROM ACUTE ORAL TOXICITY TEST, 2996 01:56:26,360 --> 01:56:30,440 COULD THAT BE USED TO WEIGH THE 2997 01:56:30,440 --> 01:56:34,880 LD 50 FOR DERMAL ACUTE SYSTEMIC 2998 01:56:34,880 --> 01:56:36,640 TOXICITY, WHAT WE FOUND THAT 2999 01:56:36,640 --> 01:56:38,840 COULD BE DONE AND EPA 3000 01:56:38,840 --> 01:56:44,640 SUBSEQUENTLY PUBLISHED A WAIVER 3001 01:56:44,640 --> 01:56:45,360 GUIDANCE. 3002 01:56:45,360 --> 01:56:46,400 NEXT, INTERESTED IN EVALUATING 3003 01:56:46,400 --> 01:56:48,040 AND CHARACTERIZING STATE OF THE 3004 01:56:48,040 --> 01:56:50,120 SCIENCE AND AVAILABLE MODELS IN 3005 01:56:50,120 --> 01:56:53,160 VITRO AND IN SILICO FOR 3006 01:56:53,160 --> 01:56:54,480 PRODUCING -- PREDICTING ACUTE 3007 01:56:54,480 --> 01:56:57,120 SYSTEMIC TOXICITY, BY THE ORAL 3008 01:56:57,120 --> 01:56:59,600 AND INHALATION ROUTES, AND BACK 3009 01:56:59,600 --> 01:57:04,440 IN 2018 A MODELING WORKSHOP WAS 3010 01:57:04,440 --> 01:57:07,440 CONVENED, A REPORT PUBLISHED, A 3011 01:57:07,440 --> 01:57:10,880 NUMBER OF MODELS, CROWD SOURCED 3012 01:57:10,880 --> 01:57:13,880 THE MATHEMATICAL AND MODELING 3013 01:57:13,880 --> 01:57:16,720 COMMUNITY TO BUILD I BELIEVE 132 3014 01:57:16,720 --> 01:57:19,000 MODELS ASSOCIATED WITH ACUTE 3015 01:57:19,000 --> 01:57:21,080 ORAL TOXICITY AND AS KAMEL 3016 01:57:21,080 --> 01:57:24,720 MANSOURI LED AN EFFORT TO BUILD 3017 01:57:24,720 --> 01:57:26,200 CONSENSUS MODEL, CATMoS, 3018 01:57:26,200 --> 01:57:28,000 SUBSEQUENTLY PUBLISHED, AND IS 3019 01:57:28,000 --> 01:57:29,720 UNDER REGULATORY CONSIDERATION 3020 01:57:29,720 --> 01:57:31,480 AS WE SPEAK. 3021 01:57:31,480 --> 01:57:32,800 AND ASSOCIATED WITH THAT A LOT 3022 01:57:32,800 --> 01:57:35,440 OF EFFORT WE'VE PUT INTO 3023 01:57:35,440 --> 01:57:36,200 CHARACTERIZING THE VARIABILITY 3024 01:57:36,200 --> 01:57:37,760 OF REFERENCE TEST METHODS, 3025 01:57:37,760 --> 01:57:39,880 RECOGNIZING THAT PERHAPS A 3026 01:57:39,880 --> 01:57:42,280 ONE-TO-ONE COMPARISON OF A NAM 3027 01:57:42,280 --> 01:57:43,400 TO TRADITIONAL REFERENCE METHOD 3028 01:57:43,400 --> 01:57:45,040 IS MAYBE NOT IDEAL BUT IF WE'RE 3029 01:57:45,040 --> 01:57:46,880 GOING TO DO THAT YOU NEED TO 3030 01:57:46,880 --> 01:57:48,200 FACTOR IN THE VARIABILITY 3031 01:57:48,200 --> 01:57:49,400 ASSOCIATED WITH THAT REFERENCE 3032 01:57:49,400 --> 01:57:50,920 METHOD BECAUSE IF THE REFERENCE 3033 01:57:50,920 --> 01:57:52,800 METHOD CAN'T REPEAT ITSELF 100% 3034 01:57:52,800 --> 01:57:54,560 OF THE TIME, YOU CAN'T POSSIBLY 3035 01:57:54,560 --> 01:57:57,320 THINK A NAM WOULD REPEAT THE 3036 01:57:57,320 --> 01:57:59,600 REFERENCE TEST METHOD 100% OF 3037 01:57:59,600 --> 01:57:59,920 THE TIME. 3038 01:57:59,920 --> 01:58:01,600 WE'VE PUBLISHED VARIABILITY 3039 01:58:01,600 --> 01:58:08,880 ANALYSIS OVER THOUSANDS OF LD 50 3040 01:58:08,880 --> 01:58:11,320 CHEMICALS TO DEMONSTRATE THAT. 3041 01:58:11,320 --> 01:58:14,920 AND JOHN HAMM LED AN EFFORT TO 3042 01:58:14,920 --> 01:58:18,520 DO A RETROSPECTIVE ANALYSIS 3043 01:58:18,520 --> 01:58:21,480 ASSOCIATED WITH GHSED A ACTIVITY 3044 01:58:21,480 --> 01:58:24,800 FORMULA, WE HAVE AVAILABLE 3045 01:58:24,800 --> 01:58:26,320 LD50s, COMBINED TO DETERMINE A 3046 01:58:26,320 --> 01:58:30,480 PREDICTED OUTCOME FOR A MIXTURE, 3047 01:58:30,480 --> 01:58:34,840 TO DEMONSTRATE THAT MANUSCRIPT 3048 01:58:34,840 --> 01:58:38,240 PUBLISHED AND UNDER 3049 01:58:38,240 --> 01:58:39,880 CONSIDERATION FOR REGULATORY 3050 01:58:39,880 --> 01:58:40,760 USE. 3051 01:58:40,760 --> 01:58:41,840 ONE OF THE FIRST THINGS WORK 3052 01:58:41,840 --> 01:58:45,120 GROUPS DO IS CATALOG AGENCY 3053 01:58:45,120 --> 01:58:47,080 NEEDS, AGAIN STARTING WITH THOSE 3054 01:58:47,080 --> 01:58:51,680 END USERS IN MIND, TO PUBLISH A 3055 01:58:51,680 --> 01:58:52,480 SCOPING DOCUMENT THAT OUTLINES 3056 01:58:52,480 --> 01:58:55,400 NOT ONLY U.S. BUT ULTIMATELY 3057 01:58:55,400 --> 01:58:56,600 INTERNATIONAL REQUIREMENTS AS 3058 01:58:56,600 --> 01:59:02,200 WELL SO WE'RE HARMONIZED 3059 01:59:02,200 --> 01:59:02,560 INTERNATIONALLY. 3060 01:59:02,560 --> 01:59:05,280 2018 PUBLISHED U.S. REQUIREMENTS 3061 01:59:05,280 --> 01:59:07,360 AND WE'VE JUST COMPLETED A DRAFT 3062 01:59:07,360 --> 01:59:08,560 OF THE INTERNATIONAL 3063 01:59:08,560 --> 01:59:10,280 REQUIREMENTS AND THAT'S BEEN 3064 01:59:10,280 --> 01:59:12,280 COMMITTED AND IS UNDER REVIEW AT 3065 01:59:12,280 --> 01:59:13,680 CRITICAL REVIEWS IN TOXICOLOGY. 3066 01:59:13,680 --> 01:59:16,240 LAST BUT NOT LEAST NICOLE 3067 01:59:16,240 --> 01:59:19,800 DETAILED THE TREMENDOUS EFFORT 3068 01:59:19,800 --> 01:59:23,120 ASSOCIATED WITH CHARACTERIZING, 3069 01:59:23,120 --> 01:59:24,720 CLEANING, CURATING INHALATION 3070 01:59:24,720 --> 01:59:25,920 DATA SAT, AND SUPER EXCITED TO 3071 01:59:25,920 --> 01:59:30,200 GET HANDS ON THAT AND DO SIMILAR 3072 01:59:30,200 --> 01:59:33,280 CROWDSOURCING EFFORT TO BUILD 3073 01:59:33,280 --> 01:59:34,920 CONSENSUS MODELS ASSOCIATED WITH 3074 01:59:34,920 --> 01:59:35,880 ACUTE INHALATION TOXICITY. 3075 01:59:35,880 --> 01:59:37,760 NEXT I'LL MOVE TO CONSIDERATION 3076 01:59:37,760 --> 01:59:39,160 OF ALTERNATIVE METHODS WORK 3077 01:59:39,160 --> 01:59:42,640 GROUP, JESSE CARTER IS HERE IN 3078 01:59:42,640 --> 01:59:44,400 THE ROOM FROM USDA, CHAIR OF 3079 01:59:44,400 --> 01:59:45,320 THAT GROUP. 3080 01:59:45,320 --> 01:59:47,480 CO-CHAIR OF THAT GROUP. 3081 01:59:47,480 --> 01:59:50,840 AND THAT GROUP HAS BEEN TASKED 3082 01:59:50,840 --> 01:59:52,400 WITH WORKING DIRECTLY WITH 3083 01:59:52,400 --> 01:59:58,400 STAKEHOLDERS TO SORT OF DEVELOP 3084 01:59:58,400 --> 02:00:01,600 THAT CATALOG OF WHAT INCENTIVES 3085 02:00:01,600 --> 02:00:03,120 COULD BE IDENTIFIED OR 3086 02:00:03,120 --> 02:00:04,760 ENCOURAGED OR PROPOSED TO CAUSE 3087 02:00:04,760 --> 02:00:09,960 FOLKS TO MORE SERIOUSLY CONSIDER 3088 02:00:09,960 --> 02:00:12,760 USE OF ALTERNATIVE METHODS. 3089 02:00:12,760 --> 02:00:14,160 ULTIMATELY THAT INVOLVES 3090 02:00:14,160 --> 02:00:15,200 REVIEWING THE REQUIREMENTS 3091 02:00:15,200 --> 02:00:15,960 ASSOCIATED WITH THE 3092 02:00:15,960 --> 02:00:18,440 CONSIDERATION OF NAMs AND HOW 3093 02:00:18,440 --> 02:00:23,160 THOSE PERHAPS MIGHT BE MODIFIED, 3094 02:00:23,160 --> 02:00:23,800 EXPANDED UPON, CERTAINLY 3095 02:00:23,800 --> 02:00:24,440 FOSTERING ADDITIONAL 3096 02:00:24,440 --> 02:00:25,080 CONSIDERATION BY STAKEHOLDERS 3097 02:00:25,080 --> 02:00:28,400 NOT THE LEAST COULD BE 3098 02:00:28,400 --> 02:00:29,760 INSTITUTIONAL ANIMAL CARE AND 3099 02:00:29,760 --> 02:00:30,800 USE COMMITTEES. 3100 02:00:30,800 --> 02:00:33,080 THE WORK GROUP WORKED WITH 3101 02:00:33,080 --> 02:00:37,240 STAKEHOLDER ORGANIZATIONS FROM A 3102 02:00:37,240 --> 02:00:40,320 VARIETY OF INDUSTRY, ACADEMIC 3103 02:00:40,320 --> 02:00:41,960 AND NON-GOVERNMENT ORGANIZATIONS 3104 02:00:41,960 --> 02:00:43,800 TO UNDERSTAND REALLY WHAT SOME 3105 02:00:43,800 --> 02:00:45,760 OF THOSE ISSUES ARE, AND YOU CAN 3106 02:00:45,760 --> 02:00:48,760 SEE A LIST OF QUESTIONS THAT HAS 3107 02:00:48,760 --> 02:00:51,600 BEEN DISCUSSED WITH THESE GROUPS 3108 02:00:51,600 --> 02:00:54,640 FROM PHARMACEUTICAL COMPANIES, 3109 02:00:54,640 --> 02:00:56,280 AGRI CHEMICALS, INDUSTRIAL 3110 02:00:56,280 --> 02:00:58,040 CHEMICALS, CONSUMER PRODUCTS. 3111 02:00:58,040 --> 02:01:00,280 LATEST STAKEHOLDERS GROUPS ARE 3112 02:01:00,280 --> 02:01:06,560 THOSE INSTITUTIONAL ANIMAL CARE 3113 02:01:06,560 --> 02:01:09,840 AND USE COMMITTEES TO UNDERSTAND 3114 02:01:09,840 --> 02:01:14,560 QUESTIONS AND INCENTIVIZE USE OF 3115 02:01:14,560 --> 02:01:15,880 NAMs, ULTIMATELY THE INTENTS 3116 02:01:15,880 --> 02:01:23,120 TO PUBLISH A SUMMARY IN WHITE 3117 02:01:23,120 --> 02:01:30,240 PAPER FORMAT. 3118 02:01:30,240 --> 02:01:31,960 ECOTOXICITY PUBLISHED AN AGENCY 3119 02:01:31,960 --> 02:01:33,600 NEEDS MANUSCRIPT TO CHARACTERIZE 3120 02:01:33,600 --> 02:01:35,680 THOSE DATA REQUIREMENTS AS 3121 02:01:35,680 --> 02:01:42,920 RELATES TO REGISTRATION AND 3122 02:01:42,920 --> 02:01:49,920 REGULATION OF CHEMICALS, IT I 3123 02:01:49,920 --> 02:01:51,640 WAS MONITORING, THE AREA IS 3124 02:01:51,640 --> 02:01:52,880 QUITE BROAD, UNDERSTANDING 3125 02:01:52,880 --> 02:01:54,720 SPECIFIC NEEDS ACROSS OUR 3126 02:01:54,720 --> 02:01:58,560 FEDERAL AGENCIES HAS REALLY BEEN 3127 02:01:58,560 --> 02:01:59,960 A YEOMAN'S TASK. 3128 02:01:59,960 --> 02:02:04,040 NOW THAT THAT WORK GROUP HAS 3129 02:02:04,040 --> 02:02:10,680 PIVOTED, FOCUSING ON IDENTIFYING 3130 02:02:10,680 --> 02:02:11,880 OR PRIORITIZING ALTERNATIVES 3131 02:02:11,880 --> 02:02:15,080 WITH FISH TOXICITY TEST, THAT 3132 02:02:15,080 --> 02:02:16,000 MANUSCRIPT IS BEING FINALIZED 3133 02:02:16,000 --> 02:02:19,320 FOR PUBLICATION, EXPECT TO SEE 3134 02:02:19,320 --> 02:02:22,920 THAT IN PEER-REVIEWED LITERATURE 3135 02:02:22,920 --> 02:02:24,280 THIS YEAR. 3136 02:02:24,280 --> 02:02:25,760 IN VITRO TO IN VIVO 3137 02:02:25,760 --> 02:02:28,960 EXTRAPOLATION, A LOT OF 3138 02:02:28,960 --> 02:02:30,400 PRODUCTIVITY FROM THAT GROUP TO 3139 02:02:30,400 --> 02:02:33,200 TAKE IN VITRO BIOACTIVE 3140 02:02:33,200 --> 02:02:34,400 CONCENTRATION AND CONTEXTUALIZE 3141 02:02:34,400 --> 02:02:35,920 INTO IN VIVO SITUATION. 3142 02:02:35,920 --> 02:02:39,680 YOU KNOW, AGAIN STARTING WITH 3143 02:02:39,680 --> 02:02:41,520 THE CATALOG OF AVAILABLE 3144 02:02:41,520 --> 02:02:43,720 METHODS, UNDERSTANDING HOW THEY 3145 02:02:43,720 --> 02:02:46,680 MIGHT BE USED, APPLIED TO 3146 02:02:46,680 --> 02:02:47,760 SPECIFIC REGULATORY QUESTIONS, 3147 02:02:47,760 --> 02:02:49,720 AND SPECIFIC RISK ASSESSMENT 3148 02:02:49,720 --> 02:02:53,480 PURPOSES THAT CAN BE ACHIEVED 3149 02:02:53,480 --> 02:02:55,640 WITH THE CURRENTLY AVAILABLE 3150 02:02:55,640 --> 02:02:57,960 APPROACHES AND OF COURSE 3151 02:02:57,960 --> 02:02:59,160 IDENTIFY GAPS, AND THAT WAS 3152 02:02:59,160 --> 02:03:01,920 PUBLICATION THAT CAME OUT IN 3153 02:03:01,920 --> 02:03:04,320 TOXICS IN 2022, RECEIVED A 3154 02:03:04,320 --> 02:03:06,800 NUMBER OF ACCOLADES OVER THE 3155 02:03:06,800 --> 02:03:10,560 PAST YEAR REALLY, RECOGNIZED BY 3156 02:03:10,560 --> 02:03:12,520 JOURNAL TOXICS AS RECOMMENDED 3157 02:03:12,520 --> 02:03:14,240 REVIEW FOR 2022, ALSO MOST 3158 02:03:14,240 --> 02:03:19,960 RECENTLY ONE OF THE CO-CHAIRS OF 3159 02:03:19,960 --> 02:03:23,360 THE IVIVE FROM ATSDR RECEIVED 3160 02:03:23,360 --> 02:03:26,000 THE -- PUBLICATION RECEIVED THE 3161 02:03:26,000 --> 02:03:27,840 2022 OUTSTANDING PUBLICATION 3162 02:03:27,840 --> 02:03:29,760 AWARD, YOU CAN SEE THE PICTURE 3163 02:03:29,760 --> 02:03:40,000 OF THE TROPHY THERE. 3164 02:03:40,000 --> 02:03:42,520 NANOMATERIALS, THIS GROUP 3165 02:03:42,520 --> 02:03:45,200 FOCUSED ALMOST SOLELY ON PULLING 3166 02:03:45,200 --> 02:03:46,720 TOGETHER NEEDS ASSOCIATINGED 3167 02:03:46,720 --> 02:03:49,600 WITH NANOMATERIALS TOX TESTING 3168 02:03:49,600 --> 02:03:52,320 AND IDENTIFYING A NUMBER OF 3169 02:03:52,320 --> 02:03:55,920 ONGOING EFFORTS, THAT CAME OUT 3170 02:03:55,920 --> 02:04:02,160 IN A PUBLICATION. 3171 02:04:02,160 --> 02:04:04,040 EXCUSE ME. 3172 02:04:04,040 --> 02:04:05,560 THIS IS ONE EXAMPLE OF A WORK 3173 02:04:05,560 --> 02:04:06,760 GROUP THEY HAVE COMPLETED THEIR 3174 02:04:06,760 --> 02:04:08,080 TASK, HAVE DONE THAT CATALOG, 3175 02:04:08,080 --> 02:04:10,160 AND AT THE BOTTOM YOU CAN SEE 3176 02:04:10,160 --> 02:04:11,800 THEY HAVE COMPLETED THEIR 3177 02:04:11,800 --> 02:04:13,200 CHARGES AND HAVE BEEN CONVERTED 3178 02:04:13,200 --> 02:04:14,320 TO EXPERT GROUP WHICH MEANS 3179 02:04:14,320 --> 02:04:17,720 THAT'S A GROUP THAT'S AVAILABLE 3180 02:04:17,720 --> 02:04:19,800 FOR CONSULTATION, IT'S AN E-MAIL 3181 02:04:19,800 --> 02:04:21,760 DISTRIBUTION LIST TO CONTACT 3182 02:04:21,760 --> 02:04:23,520 AGENCY EXPERTS IN THE AREA OF 3183 02:04:23,520 --> 02:04:24,840 NANOMATERIAL TESTING BUT COULD 3184 02:04:24,840 --> 02:04:32,320 BE REACTIVATED AT ANY POINT IN 3185 02:04:32,320 --> 02:04:33,600 DEEMED NECESSARY. 3186 02:04:33,600 --> 02:04:35,160 NICOLE ALLUDED TO EFFORTS 3187 02:04:35,160 --> 02:04:38,200 ONGOING TO UPDATE GUIDANCE FOR 3188 02:04:38,200 --> 02:04:39,400 ESTABLISHING CONFIDENCE. 3189 02:04:39,400 --> 02:04:43,000 SO THIS HAS BEEN REALLY A MUCH 3190 02:04:43,000 --> 02:04:45,000 NEEDED TASK TO UPDATE VALIDATION 3191 02:04:45,000 --> 02:04:48,040 GUIDANCE THAT WAS PUBLISHED IN 3192 02:04:48,040 --> 02:04:49,920 1997 BY ICCVAM AND I THINK WE 3193 02:04:49,920 --> 02:04:53,000 CAN ALL APPRECIATE WITH THE 3194 02:04:53,000 --> 02:04:54,160 EVOLUTION AND MODERNIZATION OF 3195 02:04:54,160 --> 02:04:56,480 TOXICOLOGY RESEARCH AND TESTING 3196 02:04:56,480 --> 02:04:59,240 THERE'S A NEED TO MODERNIZE THE 3197 02:04:59,240 --> 02:05:01,080 WAY THAT CONFIDENCE IS 3198 02:05:01,080 --> 02:05:02,480 ESTABLISHED, SO THIS WORK GROUP 3199 02:05:02,480 --> 02:05:06,520 WAS PUT TOGETHER TO DO JUST 3200 02:05:06,520 --> 02:05:07,400 THAT. 3201 02:05:07,400 --> 02:05:14,440 LED BY JOHN GORDON, SUZIE 3202 02:05:14,440 --> 02:05:16,760 FITZPATRICK AND ELIJAH PETERSEN 3203 02:05:16,760 --> 02:05:18,600 AS CHAIRS, UPDATING THE DOCUMENT 3204 02:05:18,600 --> 02:05:21,640 PUBLISH THE IN 1997 BASED ON 3205 02:05:21,640 --> 02:05:23,080 PRINCIPLES FROM OECD GUIDANCE 3206 02:05:23,080 --> 02:05:25,240 DOCUMENT 34, THOSE WILL REMAIN 3207 02:05:25,240 --> 02:05:30,320 THE SAME IN THE NEW GUIDANCE BUT 3208 02:05:30,320 --> 02:05:31,720 IMPORTANTLY INTRODUCING THAT 3209 02:05:31,720 --> 02:05:34,040 CONTEXT OF USE TERMINOLOGY INTO 3210 02:05:34,040 --> 02:05:36,440 THIS DOCUMENT THAT'S SO NEEDED 3211 02:05:36,440 --> 02:05:40,560 AND IMPORTANT IN THESE 3212 02:05:40,560 --> 02:05:40,880 EVALUATIONS. 3213 02:05:40,880 --> 02:05:51,400 AND WE'VE HEARD A LOT ABOUT A 3214 02:05:53,560 --> 02:05:54,920 WONDERFUL PAPER VANDERSONE, 3215 02:05:54,920 --> 02:05:56,320 ESTABLISHING CONFIDENCE AND 3216 02:05:56,320 --> 02:05:58,440 GUIDING PRINCIPLES, AND UPDATED 3217 02:05:58,440 --> 02:05:59,840 FIGURE ADAPTED FROM THAT THAT 3218 02:05:59,840 --> 02:06:04,280 WILL BE INCLUDED IN THE NEW 3219 02:06:04,280 --> 02:06:07,280 ICCVAM GUIDANCE FOCUSING ON USE 3220 02:06:07,280 --> 02:06:12,000 OF EFFICIENT, FLEXIBLE, ROBUST 3221 02:06:12,000 --> 02:06:14,360 PRACTICES, DELINEATING CONTEXT 3222 02:06:14,360 --> 02:06:16,480 REQUIREMENTS, PROMOTING NEW 3223 02:06:16,480 --> 02:06:19,200 APPROACHES FOR ESTABLISHING 3224 02:06:19,200 --> 02:06:19,840 CONFIDENCE, AND IMPORTANTLY 3225 02:06:19,840 --> 02:06:21,080 UTILIZING PUBLIC/PRIVATE 3226 02:06:21,080 --> 02:06:22,800 PARTNERSHIPS THAT WE'VE SEEN SO 3227 02:06:22,800 --> 02:06:24,600 PRODUCTIVE OVER THE PAST FEW 3228 02:06:24,600 --> 02:06:27,000 YEARS WITH ENGAGING DIRECTLY 3229 02:06:27,000 --> 02:06:28,200 WITH STAKEHOLDER ORGANIZATIONS 3230 02:06:28,200 --> 02:06:29,160 TO UNDERSTAND THEIR CHALLENGES 3231 02:06:29,160 --> 02:06:31,520 AND ALLOW THEM THE OPPORTUNITY 3232 02:06:31,520 --> 02:06:33,880 TO UNDERSTAND SPECIFIC NEEDS 3233 02:06:33,880 --> 02:06:35,960 FROM THE FEDERAL AGENCIES. 3234 02:06:35,960 --> 02:06:38,040 SO THE DRAFT DOCUMENT IS 3235 02:06:38,040 --> 02:06:39,680 CURRENTLY UNDERGOING AGENCY 3236 02:06:39,680 --> 02:06:41,480 CLEARANCE PROCESSES AS WE SPEAK. 3237 02:06:41,480 --> 02:06:42,720 OUR ANTICIPATION IS THOSE 3238 02:06:42,720 --> 02:06:45,040 PROCESSES WILL BE DONE LATER 3239 02:06:45,040 --> 02:06:47,320 THIS SUMMER, AND IMPORTANT FOR 3240 02:06:47,320 --> 02:06:49,400 THIS GROUP THERE WILL BE A 3241 02:06:49,400 --> 02:06:51,680 PUBLIC COMMENT PERIOD FOR THE 3242 02:06:51,680 --> 02:06:53,360 DOCUMENT WE HOPE WILL HAPPEN ON 3243 02:06:53,360 --> 02:06:53,960 OR ABOUT MID-JULY. 3244 02:06:53,960 --> 02:06:56,760 SO STAY TUNED FOR THAT. 3245 02:06:56,760 --> 02:06:59,800 AND THAT WILL GO OUT THROUGH A 3246 02:06:59,800 --> 02:07:00,880 VARIETY OF COMMUNICATION 3247 02:07:00,880 --> 02:07:02,000 CHALLENGES NOT THE LEAST OF 3248 02:07:02,000 --> 02:07:04,240 WHICH IS THE NICEATM LISTSERV 3249 02:07:04,240 --> 02:07:06,160 THAT NICOLE ALLUDED TO EARLY. 3250 02:07:06,160 --> 02:07:08,800 LAST BUT NOT LEAST I MENTIONED A 3251 02:07:08,800 --> 02:07:11,280 NEW WORK GROUP THAT HAS JUST 3252 02:07:11,280 --> 02:07:15,800 BEEN FORMED VIA LAST ICCVAM 3253 02:07:15,800 --> 02:07:16,520 MEETING. 3254 02:07:16,520 --> 02:07:19,840 REALLY SPONSORED BY DoD, EPA, 3255 02:07:19,840 --> 02:07:20,000 FDA. 3256 02:07:20,000 --> 02:07:22,560 RECOGNIZING THE NEED WITH ALL 3257 02:07:22,560 --> 02:07:25,640 THE AREAS OF CHALLENGES AND 3258 02:07:25,640 --> 02:07:26,600 INTEREST AND TESTING NEEDS 3259 02:07:26,600 --> 02:07:31,320 ACROSS A NUMBER OF AGENCIES, THE 3260 02:07:31,320 --> 02:07:33,480 PERVASIVE NATURE OF THESE 3261 02:07:33,480 --> 02:07:35,240 COMPOUNDS ACROSS SO MANY 3262 02:07:35,240 --> 02:07:39,240 DIFFERENT SECTORS AND TYPES OF 3263 02:07:39,240 --> 02:07:41,600 CHEMICALS, NEED TO IDENTIFY HOW 3264 02:07:41,600 --> 02:07:48,720 TO APPLY NAMs IN EVALUATING 3265 02:07:48,720 --> 02:07:52,000 TOXICITIES, BECAUSE AT PRESENT 3266 02:07:52,000 --> 02:07:53,320 THEY ARE NOT BROADLY BEING 3267 02:07:53,320 --> 02:07:54,280 APPLIED AND THE COMMITTEE 3268 02:07:54,280 --> 02:07:55,760 RECOGNIZES THERE'S A NEED FOR 3269 02:07:55,760 --> 02:07:56,800 DIRECT INPUT THERE. 3270 02:07:56,800 --> 02:07:58,760 SO THAT WORK GROUP SCOPE AND 3271 02:07:58,760 --> 02:08:00,200 CHARGE IS UNDER DEVELOPMENT AS 3272 02:08:00,200 --> 02:08:00,880 WE SPEAK. 3273 02:08:00,880 --> 02:08:03,040 SO I WON'T PRESENT THAT PUBLICLY 3274 02:08:03,040 --> 02:08:05,440 TODAY BUT YOU CAN LOOK FORWARD 3275 02:08:05,440 --> 02:08:07,120 AT THE MEETING THIS FALL WHEN I 3276 02:08:07,120 --> 02:08:12,160 EXPECT THAT TO BE REFINED. 3277 02:08:12,160 --> 02:08:14,440 I WILL CLOSE WITH INVITING ANY 3278 02:08:14,440 --> 02:08:14,800 QUESTIONS. 3279 02:08:14,800 --> 02:08:15,160 THANKS. 3280 02:08:15,160 --> 02:08:17,720 [APPLAUSE] 3281 02:08:17,720 --> 02:08:23,720 3282 02:08:23,720 --> 02:08:26,920 3283 02:08:26,920 --> 02:08:29,640 >> ARE THERE ANY QUESTIONS IN 3284 02:08:29,640 --> 02:08:31,520 THE ROOM FOR DAVE? 3285 02:08:31,520 --> 02:08:34,240 THERE IS A QUESTION THAT HAS 3286 02:08:34,240 --> 02:08:38,600 COME THROUGH ONLINE FOR MYSELF 3287 02:08:38,600 --> 02:08:41,560 AND/OR DAVE. 3288 02:08:41,560 --> 02:08:44,840 FROM KATHERINE PAGE, ALSO 3289 02:08:44,840 --> 02:08:45,480 SCIENTIFIC ADVISORY COMMITTEE, 3290 02:08:45,480 --> 02:08:48,240 ARE THERE PLANS TO ADAPT ACUTE 3291 02:08:48,240 --> 02:08:53,720 INHALATION ACUTE TOXICITY WORK 3292 02:08:53,720 --> 02:08:54,080 TO MIXTURES? 3293 02:08:54,080 --> 02:08:57,560 SO THE FIRST THING I'LL SAY WE 3294 02:08:57,560 --> 02:09:02,080 HAVE NOT YET BEEN ABLE TO ADAPT 3295 02:09:02,080 --> 02:09:05,880 THE ACUTE ORAL SYSTEMIC TOXICITY 3296 02:09:05,880 --> 02:09:07,520 APPROACH FROM THE IN SILICO 3297 02:09:07,520 --> 02:09:09,040 PERSPECTIVE TO MIXTURES YET 3298 02:09:09,040 --> 02:09:11,360 ALTHOUGH I DIDN'T SHOW IT BUT 3299 02:09:11,360 --> 02:09:13,120 THERE WAS A PUBLICATION FROM OUR 3300 02:09:13,120 --> 02:09:16,040 U.S. AIR FORCE COLLEAGUES THAT I 3301 02:09:16,040 --> 02:09:18,440 ACTUALLY EVALUATED THE ABILITY 3302 02:09:18,440 --> 02:09:27,080 OF USING CATMoS TO PREDICT 3303 02:09:27,080 --> 02:09:28,840 ORAL LD50 FOR MIXTURES 3304 02:09:28,840 --> 02:09:30,720 COMPONENTS AND ADD TO PREDICT 3305 02:09:30,720 --> 02:09:34,440 LD50 OF THE MIXTURE AND FOUNT IT 3306 02:09:34,440 --> 02:09:36,360 WAS VERY EFFECTIVE AND RELIABLE. 3307 02:09:36,360 --> 02:09:39,240 SO OUR HOPE IS THAT THAT 3308 02:09:39,240 --> 02:09:40,880 FOUNDATIONAL WORK COULD MAYBE 3309 02:09:40,880 --> 02:09:42,720 HELP MOVE THAT FORWARD TO 3310 02:09:42,720 --> 02:09:49,160 ACCEPTANCE OF AN IN SILICO 3311 02:09:49,160 --> 02:09:50,120 APPROACH TO PREDICTING LD 50 OF 3312 02:09:50,120 --> 02:09:51,040 A MIXTURE. 3313 02:09:51,040 --> 02:09:53,720 NO REASON WE COULDN'T TAKE THAT 3314 02:09:53,720 --> 02:09:56,120 APPROACH WITH LC50s AND ACUTE 3315 02:09:56,120 --> 02:09:57,640 INHALATION TOXICITY AS WELL. 3316 02:09:57,640 --> 02:10:01,840 THE FIRST STEP WOULD BE GETTING 3317 02:10:01,840 --> 02:10:05,120 RECOGNITION WITH THE LD 50s IF 3318 02:10:05,120 --> 02:10:07,920 HAVE EXPERIMENTAL VALUES YOU CAN 3319 02:10:07,920 --> 02:10:13,960 USE GHS APPROACH TO CALCULATE 3320 02:10:13,960 --> 02:10:18,240 APPLYING TO LC 50 AND COMBINE 3321 02:10:18,240 --> 02:10:19,680 THE PREDICTED LC50 TO PREDICT 3322 02:10:19,680 --> 02:10:20,560 THE MIXTURE. 3323 02:10:20,560 --> 02:10:23,000 I THINK THE OTHER EXCITING AREA 3324 02:10:23,000 --> 02:10:25,920 THAT HAS A LOT OF POTENTIAL IN 3325 02:10:25,920 --> 02:10:27,040 UNDERSTANDING INHALATION 3326 02:10:27,040 --> 02:10:31,080 TOXICITY OF MIXTURES ARE SOME OF 3327 02:10:31,080 --> 02:10:32,160 THE EXPERIMENTAL PLATFORMS THAT 3328 02:10:32,160 --> 02:10:35,560 DTT AND OTHERS ARE INVESTIGATING 3329 02:10:35,560 --> 02:10:38,120 USING AIR LIQUID INTERFACE 3330 02:10:38,120 --> 02:10:45,960 MODELS AND SOME EXPOSURE CHAMBER 3331 02:10:45,960 --> 02:10:50,000 SYSTEMS THAT CAN ALLOW TO DEFINE 3332 02:10:50,000 --> 02:10:53,600 TO UNDERSTAND IN IN VITRO SYSTEM 3333 02:10:53,600 --> 02:10:54,280 AS WELL. 3334 02:10:54,280 --> 02:10:56,800 DAVE, WE HAVE ANOTHER QUESTION 3335 02:10:56,800 --> 02:10:57,040 ONLINE. 3336 02:10:57,040 --> 02:10:59,640 >> YEAH, THERE'S A COMMENT FOR 3337 02:10:59,640 --> 02:11:07,400 YOU, NICOLE, FROM AMY KYLE. 3338 02:11:07,400 --> 02:11:08,480 IMPORTANT TO ENGAGE COMMUNITIES 3339 02:11:08,480 --> 02:11:11,320 TO IDENTIFY WHETHER DATA SOURCES 3340 02:11:11,320 --> 02:11:12,360 REPRESENT ELEMENTS THEY VIEW AS 3341 02:11:12,360 --> 02:11:15,160 MOST IMPORTANT. 3342 02:11:15,160 --> 02:11:16,920 FOR EXAMPLE, IS A COUNTY LEVEL 3343 02:11:16,920 --> 02:11:18,360 SCALE APPROPRIATE? 3344 02:11:18,360 --> 02:11:21,600 THE PRESENTATION OUTLINED MORE 3345 02:11:21,600 --> 02:11:22,440 AUTOMATED APPROACHES TO 3346 02:11:22,440 --> 02:11:24,560 INTEGRATING -- THAT WAS JUST A 3347 02:11:24,560 --> 02:11:25,640 COMMENT FROM AMY, EXCUSE ME. 3348 02:11:25,640 --> 02:11:27,600 WE HAVE ANOTHER QUESTION THAT 3349 02:11:27,600 --> 02:11:28,240 SAYS THE PRESENTATION -- 3350 02:11:28,240 --> 02:11:30,240 >>THANK YOU FOR YOUR COMMENT, 3351 02:11:30,240 --> 02:11:31,800 AMY, WE'LL BE FOLLOWING UP 3352 02:11:31,800 --> 02:11:33,960 OFFLINE ON THAT COMMENT AND SOME 3353 02:11:33,960 --> 02:11:36,480 COMMENTS FROM THE PUBLIC 3354 02:11:36,480 --> 02:11:37,840 COMMENTING PERIOD. 3355 02:11:37,840 --> 02:11:39,320 >> YOUR PRESENTATION OUTLINED 3356 02:11:39,320 --> 02:11:41,200 MORE AUTOMATED APPROACHES TO 3357 02:11:41,200 --> 02:11:45,040 INTEGRATING NEW DATA INTO NIEHS 3358 02:11:45,040 --> 02:11:49,160 CURATE THE DATA SOURCE, I'M 3359 02:11:49,160 --> 02:11:51,040 WONDERING ABOUT LINKING TO 3360 02:11:51,040 --> 02:11:53,040 AGENCY ACTIONS AT EPA FOR 3361 02:11:53,040 --> 02:11:54,880 EXAMPLE, IS THERE CONSIDERATION 3362 02:11:54,880 --> 02:11:56,400 OF FLAGGING RESEARCH RESULTS 3363 02:11:56,400 --> 02:12:04,280 THAT WOULD SUGGEST NEED TO 3364 02:12:04,280 --> 02:12:05,600 UPDATE REFERENCE VALUES IN RIGHT 3365 02:12:05,600 --> 02:12:07,320 NOW THEY ARE RARELY UPDATED, 3366 02:12:07,320 --> 02:12:08,760 COULD WE BUILT A SYSTEM THAT 3367 02:12:08,760 --> 02:12:11,280 LINKS NEW FINDINGS FROM THE 3368 02:12:11,280 --> 02:12:12,080 SCIENCE COMMUNITY TO THE 3369 02:12:12,080 --> 02:12:13,920 REGULATORY COMMUNITY IN REAL 3370 02:12:13,920 --> 02:12:16,000 TIME, NOT NECESSARILY WAITING 3371 02:12:16,000 --> 02:12:19,280 UNTIL THE NEXT SYSTEMATIC REVIEW 3372 02:12:19,280 --> 02:12:19,640 OR OTHER PROMPT? 3373 02:12:19,640 --> 02:12:20,680 >> A REALLY INTERESTING 3374 02:12:20,680 --> 02:12:20,920 QUESTION. 3375 02:12:20,920 --> 02:12:24,320 THERE'S A LOT OF LAYERS IN THAT 3376 02:12:24,320 --> 02:12:25,840 QUESTION. 3377 02:12:25,840 --> 02:12:26,760 AND EXCELLENT SUGGESTIONS, 3378 02:12:26,760 --> 02:12:28,040 HIDDEN WITHIN THE QUESTION FORM 3379 02:12:28,040 --> 02:12:31,120 AS WELL. 3380 02:12:31,120 --> 02:12:37,800 I KNOW THAT CPHEA AND IRIS UNDER 3381 02:12:37,800 --> 02:12:40,640 LEADERSHIP OF CHRIS THAYER HAS 3382 02:12:40,640 --> 02:12:43,680 MODERNIZED APPROACHES TO 3383 02:12:43,680 --> 02:12:44,800 SYSTEMATIC REVIEWS AND 3384 02:12:44,800 --> 02:12:46,760 INCORPORATING MORE AUTOMATION 3385 02:12:46,760 --> 02:12:51,040 AND MORE A.I.-ENABLED METHODS OF 3386 02:12:51,040 --> 02:12:52,680 ASSESSING STUDY QUALITY AND 3387 02:12:52,680 --> 02:12:53,520 INTEGRATING ADDITIONAL 3388 02:12:53,520 --> 02:12:55,520 SCIENTIFIC DATA AND LITERATURE 3389 02:12:55,520 --> 02:12:59,440 STUDIES, INTO THEIR VERY 3390 02:12:59,440 --> 02:13:00,960 COMPREHENSIVE ASSESSMENTS, SO WE 3391 02:13:00,960 --> 02:13:02,400 ARE IN VERY CLOSE COMMUNICATION 3392 02:13:02,400 --> 02:13:05,600 WITH THAT GROUP AND SOME OTHER 3393 02:13:05,600 --> 02:13:06,360 REGULATORY DECISION MAKING 3394 02:13:06,360 --> 02:13:08,400 COLLEAGUES TO ENSURE THAT THE 3395 02:13:08,400 --> 02:13:11,400 WORK THAT WE'RE DOING WILL 3396 02:13:11,400 --> 02:13:13,800 SUPPORT EXACTLY WHAT'S BEING 3397 02:13:13,800 --> 02:13:14,320 PREPAREDDED, MORE RAPID 3398 02:13:14,320 --> 02:13:16,000 INTEGRATION OF INFORMATION FROM 3399 02:13:16,000 --> 02:13:17,480 THE SCIENTIFIC LITERATURE THAT 3400 02:13:17,480 --> 02:13:22,000 IS RELIABLE AND OF HIGH QUALITY 3401 02:13:22,000 --> 02:13:24,160 TO UPDATE REGULATORY VALUES. 3402 02:13:24,160 --> 02:13:26,480 THANK YOU FOR THAT. 3403 02:13:26,480 --> 02:13:27,920 >> ONE LAST QUESTION THAT'S 3404 02:13:27,920 --> 02:13:33,480 RELATED TO ORGANS ON THE CHIPE 3405 02:13:33,480 --> 02:13:35,880 BEST TO SAVE AFTER THE BREAK 3406 02:13:35,880 --> 02:13:37,000 AFTER TWO PRESENTATIONS 3407 02:13:37,000 --> 02:13:38,040 ASSOCIATINGED WITH THAT 3408 02:13:38,040 --> 02:13:38,400 TECHNOLOGY. 3409 02:13:38,400 --> 02:13:38,680 >> PERFECT. 3410 02:13:38,680 --> 02:13:39,400 EXCELLENT QUESTIONS. 3411 02:13:39,400 --> 02:13:48,040 ONE IN THE ROOM. 3412 02:13:48,040 --> 02:13:48,200 YEP. 3413 02:13:48,200 --> 02:13:54,560 >> THANK YOU, DAVE. 3414 02:13:54,560 --> 02:13:57,440 FIRST A PLUG FOR GOOD IN VITRO 3415 02:13:57,440 --> 02:13:58,520 PRACTICES, A QUESTION TOO. 3416 02:13:58,520 --> 02:14:00,160 THE GOOD IN VITRO METHOD 3417 02:14:00,160 --> 02:14:03,000 PRACTICES WERE BROUGHT ABOUT 3418 02:14:03,000 --> 02:14:05,880 BECAUSE OF THE CHALLENGES IN 3419 02:14:05,880 --> 02:14:08,160 HAVING LESS THAN STELLAR 3420 02:14:08,160 --> 02:14:10,680 CONFIDENCE AFTER SUBSTANTIAL 3421 02:14:10,680 --> 02:14:11,600 VALIDATION STUDIES CONDUCTED, 3422 02:14:11,600 --> 02:14:15,680 GOING BACK OVER THE LAST 20 OR 3423 02:14:15,680 --> 02:14:17,040 30 YEARS, AND AFTER INVESTING 3424 02:14:17,040 --> 02:14:19,240 QUITE A BIT AND SEVERAL HUNDRED 3425 02:14:19,240 --> 02:14:24,320 CHEMICALS, MULTIPLE 3426 02:14:24,320 --> 02:14:27,400 LABORATORIES, SEVERAL REASONS 3427 02:14:27,400 --> 02:14:29,040 FOR FAILURES, SOME HE TEST 3428 02:14:29,040 --> 02:14:33,880 METHODS NOT PLANNED FROM 3429 02:14:33,880 --> 02:14:34,400 RELEVANCE PERSPECTIVE FOR 3430 02:14:34,400 --> 02:14:37,800 BIOLOGICAL RELEVANCE OR PURPOSE. 3431 02:14:37,800 --> 02:14:41,400 ALSO RELIABILITY, WE FOUND THAT 3432 02:14:41,400 --> 02:14:45,000 RELIABILITY QUESTIONS CAME UP. 3433 02:14:45,000 --> 02:14:47,000 MANY PRESENTATIONS, EXCELLENT 3434 02:14:47,000 --> 02:14:47,760 PRESENTATIONS, MANY FOCUSED ON 3435 02:14:47,760 --> 02:14:51,040 HOW DO YOU GAIN CONFIDENCE IN 3436 02:14:51,040 --> 02:15:01,600 TEST METHODS, AND REALLY 3437 02:15:01,600 --> 02:15:05,720 APPRECIATE ELIJAH PETERSENS 3438 02:15:05,720 --> 02:15:07,240 METHOD, ONE ON PIPETTING. 3439 02:15:07,240 --> 02:15:08,880 WE TAKE FOR GRANTED WE CAN 3440 02:15:08,880 --> 02:15:11,040 PIPETTE, RIGHT? 3441 02:15:11,040 --> 02:15:15,360 AND THE GLPs SAY, OKAY, IF YOU 3442 02:15:15,360 --> 02:15:18,400 HAVE METHODS TO PIPETTE 100 3443 02:15:18,400 --> 02:15:20,040 MICRO LITERS MINUS, YOU NEED 3444 02:15:20,040 --> 02:15:22,120 DOCUMENTATION TO SHOW THAT. 3445 02:15:22,120 --> 02:15:25,400 WHAT'S GOOD, IT FORCES A 3446 02:15:25,400 --> 02:15:25,960 PERSON'S -- TEST METHOD 3447 02:15:25,960 --> 02:15:26,920 DEVELOPERS, TO THINK ABOUT 3448 02:15:26,920 --> 02:15:29,520 CRITICAL POINTS IN THE TEST 3449 02:15:29,520 --> 02:15:33,120 METHOD EARLY ON, 100 MICRO 3450 02:15:33,120 --> 02:15:36,120 LITERS PLUS MINUS 1 SUFFICIENT, 3451 02:15:36,120 --> 02:15:38,880 APPROPRIATE, HOW DOES IT IMPACT, 3452 02:15:38,880 --> 02:15:42,680 WHAT OTHER COMPONENTS? 3453 02:15:42,680 --> 02:15:44,120 CELL SYSTEM, OR THE TEST TO BE 3454 02:15:44,120 --> 02:15:47,360 EVALUATED, SO ON, BUT ON 3455 02:15:47,360 --> 02:15:49,680 RELIABILITY SIDE YOU ASK WHAT 3456 02:15:49,680 --> 02:15:56,800 ARE THE CONSEQUENCES OF 3457 02:15:56,800 --> 02:15:57,240 VARIABILITY. 3458 02:15:57,240 --> 02:15:59,960 GOOD PRACTICES FORCE A PERSON TO 3459 02:15:59,960 --> 02:16:00,960 CHARACTERIZE QUALITY OF TEST 3460 02:16:00,960 --> 02:16:01,720 METHOD AHEAD OF TIME. 3461 02:16:01,720 --> 02:16:03,560 ONE OF THE THINGS WE FOUND 3462 02:16:03,560 --> 02:16:05,120 RECENTLY AS WE'VE BEEN TALKING 3463 02:16:05,120 --> 02:16:07,400 ABOUT GOOD IN VITRO METHOD 3464 02:16:07,400 --> 02:16:11,320 PRACTICES THERE SEEMS TO BE 3465 02:16:11,320 --> 02:16:12,880 GUIDELINES OR DOCUMENTS FIVE 3466 02:16:12,880 --> 02:16:18,000 YEARS BACK AND SEEMS TO BE QUITE 3467 02:16:18,000 --> 02:16:23,480 A BIT OF NAIVETE, SO I'LL PUT IN 3468 02:16:23,480 --> 02:16:28,400 AN APOLOGY, A PLUG FOR SERVICES 3469 02:16:28,400 --> 02:16:31,440 TO REVIEW FRAMEWORK WITH 3470 02:16:31,440 --> 02:16:33,560 PERSPECTIVE TEST METHOD 3471 02:16:33,560 --> 02:16:34,960 DEVELOPERS AND DOWNSTREAM TO 3472 02:16:34,960 --> 02:16:37,920 PROVIDE AN EVALUATION OF GOOD IN 3473 02:16:37,920 --> 02:16:39,680 VITRO METHOD PRACTICES AS A TOOL 3474 02:16:39,680 --> 02:16:42,400 TO HELP THEM BUILD THOSE TYPE OF 3475 02:16:42,400 --> 02:16:45,560 CRITERIA AND TEST METHODS OR 3476 02:16:45,560 --> 02:16:46,200 APPLICATIONS. 3477 02:16:46,200 --> 02:16:48,800 BUT THE SECOND PART COMES TO A 3478 02:16:48,800 --> 02:16:51,640 QUESTION HERE, HOW AS WE MOVE 3479 02:16:51,640 --> 02:16:54,480 FORWARD WITH REVIEWING GUIDANCE 3480 02:16:54,480 --> 02:16:57,000 DOCUMENT 34 HOW WOULD REGULATORY 3481 02:16:57,000 --> 02:16:58,000 AGENCIES SEE THEMSELVES FITTING 3482 02:16:58,000 --> 02:17:00,400 IN GOOD IN VITRO METHOD 3483 02:17:00,400 --> 02:17:02,800 PRACTICES AS A CRITERIA PRIOR TO 3484 02:17:02,800 --> 02:17:06,960 ACCEPTING TEST METHODS FOR 3485 02:17:06,960 --> 02:17:07,240 VALIDATION? 3486 02:17:07,240 --> 02:17:11,000 >> THANK YOU, HANS, FOR THE 3487 02:17:11,000 --> 02:17:12,520 INFORMATIVE COMMENT/QUESTION. 3488 02:17:12,520 --> 02:17:14,200 I THINK THAT THE GOOD IN VITRO 3489 02:17:14,200 --> 02:17:17,480 METHODS PRACTICES IS A REALLY 3490 02:17:17,480 --> 02:17:19,520 OUTSTANDING RESOURCE, AND IT'S 3491 02:17:19,520 --> 02:17:25,120 ONE THAT WE CITE HEAVILY IN 3492 02:17:25,120 --> 02:17:26,440 ICCVAM VALIDATION GUIDANCE THAT 3493 02:17:26,440 --> 02:17:28,280 DAVE MENTIONED IN HIS 3494 02:17:28,280 --> 02:17:30,280 PRESENTATION, CURRENTLY IN FINAL 3495 02:17:30,280 --> 02:17:31,800 DRAFT FORM, GOING THROUGH 3496 02:17:31,800 --> 02:17:33,480 CLEARANCE AT 17 AGENCIES, WE 3497 02:17:33,480 --> 02:17:34,480 ANTICIPATE OUT FOR PUBLIC 3498 02:17:34,480 --> 02:17:35,560 COMMENT IN JULY. 3499 02:17:35,560 --> 02:17:37,640 SO IF YOU READ IT IN JULY AND 3500 02:17:37,640 --> 02:17:39,960 FEEL LIKE THERE'S NOT ENOUGH 3501 02:17:39,960 --> 02:17:43,800 TECHNICAL INFORMATION THEIR -- 3502 02:17:43,800 --> 02:17:45,280 OR THAT WE NEED ADDITIONAL 3503 02:17:45,280 --> 02:17:47,800 DETAILS IN THAT AREA SUBMIT THAT 3504 02:17:47,800 --> 02:17:48,520 THROUGH PUBLIC COMMENT. 3505 02:17:48,520 --> 02:17:49,680 IT'S ALSO SOMETHING THAT'S 3506 02:17:49,680 --> 02:17:51,880 ABSOLUTELY FEEDING INTO THE 3507 02:17:51,880 --> 02:17:58,760 PROJECT ON REVISION OF GD 34 AT 3508 02:17:58,760 --> 02:18:01,160 OECD DOCUMENT TOO AND JRC WAS 3509 02:18:01,160 --> 02:18:04,600 INVOLVED AND CO-LEADING REVISION 3510 02:18:04,600 --> 02:18:06,000 OF GD 34 WITH US AND WE INTEND 3511 02:18:06,000 --> 02:18:09,600 TO HAVE ALL OF OUR ICCVAM 3512 02:18:09,600 --> 02:18:10,360 REGULATORY PARTNERS ALSO 3513 02:18:10,360 --> 02:18:14,080 CONTRIBUTING TO THE REVISION OF 3514 02:18:14,080 --> 02:18:16,920 GD 34 AND ADVISING US ON THAT AS 3515 02:18:16,920 --> 02:18:17,680 WELL. 3516 02:18:17,680 --> 02:18:18,880 THANK YOU. 3517 02:18:18,880 --> 02:18:19,760 >> THANK YOU. 3518 02:18:19,760 --> 02:18:21,200 >> OKAY. 3519 02:18:21,200 --> 02:18:23,280 I HAVE 11:25. 3520 02:18:23,280 --> 02:18:24,720 WE'LL TAKE A FIVE-MINUTE BREAK 3521 02:18:24,720 --> 02:18:25,800 BECAUSE WE'RE BEHIND SCHEDULE. 3522 02:18:25,800 --> 02:18:28,520 SO WE'LL TAKE A FIVE-MINUTE 3523 02:18:28,520 --> 02:18:33,000 BREAK, RECONVENE AT 11:30, SO 3524 02:18:33,000 --> 02:18:34,120 FOR THOSE ONLINE WE WILL BE BACK 3525 02:18:34,120 --> 02:18:39,600 IN FIVE MINUTES. 3526 02:18:39,600 --> 02:18:44,440 CONTINUING ALONG, EXCITED ABOUT 3527 02:18:44,440 --> 02:18:45,560 THIS LAST SESSION. 3528 02:18:45,560 --> 02:18:48,720 WE HAVE EXCELLENT TALKS. 3529 02:18:48,720 --> 02:18:53,200 FIRST IS FROM USDA AWIC, 3530 02:18:53,200 --> 02:18:57,160 PRESENTED BY JESSIE CARTER. 3531 02:18:57,160 --> 02:18:59,240 >> HOPE YOU ENJOYED THE SHORT 3532 02:18:59,240 --> 02:18:59,560 BREAK. 3533 02:18:59,560 --> 02:19:02,080 I'LL BE TALKING ABOUT THE ANIMAL 3534 02:19:02,080 --> 02:19:03,360 WELFARE INFORMATION CENTER, A 3535 02:19:03,360 --> 02:19:08,000 PART OF THE NATIONAL 3536 02:19:08,000 --> 02:19:09,120 AGRICULTURAL LIBRARY. 3537 02:19:09,120 --> 02:19:10,520 IT'S DIFFERENT THAN WHAT YOU 3538 02:19:10,520 --> 02:19:12,080 HEARD EARLIER, A LOT OF 3539 02:19:12,080 --> 02:19:15,440 PRESENTERS FOCUS ON RESEARCH IN 3540 02:19:15,440 --> 02:19:18,120 THIS AREA BUT WE'RE MORE THE 3541 02:19:18,120 --> 02:19:24,200 INFORMATION ARM OF THE USDA. 3542 02:19:24,200 --> 02:19:26,160 I'LL TALK HOW WE HELP PEOPLE 3543 02:19:26,160 --> 02:19:36,280 FIND INFORMATION ON NAMs AND 3544 02:19:36,280 --> 02:19:45,520 RESEARCH ALTERNATIVES. 3545 02:19:45,520 --> 02:19:55,560 3546 02:19:58,520 --> 02:20:01,240 >> I'M GOING TO GIVE CONTEXT OF 3547 02:20:01,240 --> 02:20:02,880 THE ANIMAL WELFARE INFORMATION 3548 02:20:02,880 --> 02:20:07,160 CENTER, LOCATED AT THE NATIONAL 3549 02:20:07,160 --> 02:20:11,280 AGRICULTURAL LIBRARY, IN 3550 02:20:11,280 --> 02:20:12,160 FELTSVILLE MARYLAND, CREATED IN 3551 02:20:12,160 --> 02:20:15,680 1862 BY THE SIGNING OF THE 3552 02:20:15,680 --> 02:20:17,520 ORGANIC ACT WITH PRESIDENT 3553 02:20:17,520 --> 02:20:20,680 LINCOLN, AND THE MISSION IS TO 3554 02:20:20,680 --> 02:20:22,360 FACILITATE CREATION OF 3555 02:20:22,360 --> 02:20:24,880 AGRICULTURAL KNOWLEDGE THROUGH 3556 02:20:24,880 --> 02:20:25,640 ACQUISITION, CURATION, 3557 02:20:25,640 --> 02:20:26,960 DISSEMINATION OF INFORMATION 3558 02:20:26,960 --> 02:20:28,160 NEEDED TO SOLVE AGRICULTURAL 3559 02:20:28,160 --> 02:20:31,240 CHALLENGES TODAY AND IN THE 3560 02:20:31,240 --> 02:20:32,320 FUTURE. 3561 02:20:32,320 --> 02:20:36,080 AND THERE ARE EIGHT INFORMATION 3562 02:20:36,080 --> 02:20:37,120 CENTERS AT NAL, SUBJECT MATTER 3563 02:20:37,120 --> 02:20:41,200 BASED, ONE BEING THE ANIMAL 3564 02:20:41,200 --> 02:20:42,760 WELFARE INFORMATION CENTER. 3565 02:20:42,760 --> 02:20:46,240 SO IT WAS CREATED OUT OF THE 3566 02:20:46,240 --> 02:20:48,640 1985 ANIMAL WELFARE ACT 3567 02:20:48,640 --> 02:20:50,280 AMENDMENT, THAT FOCUSED ON 3568 02:20:50,280 --> 02:20:52,360 ANIMAL CARE IN USE AND RESEARCH, 3569 02:20:52,360 --> 02:20:55,760 MINIMIZING PAIN AND DISTRESS TO 3570 02:20:55,760 --> 02:20:56,960 ANIMALS IN RESEARCH. 3571 02:20:56,960 --> 02:21:04,960 THE REASON THIS CAME ABOUT, 3572 02:21:04,960 --> 02:21:07,920 AWIC, P.I.s WOULD BE ASKED TO 3573 02:21:07,920 --> 02:21:09,520 CONSIDER ALTERNATIVE TO PAINFUL 3574 02:21:09,520 --> 02:21:12,840 PROCEDURES THAT CONGRESS THOUGHT 3575 02:21:12,840 --> 02:21:15,240 IT WAS IMPERATIVE TO PUT AN 3576 02:21:15,240 --> 02:21:16,440 INFORMATION SERVICE TO PROVIDE 3577 02:21:16,440 --> 02:21:17,360 INFORMATION PERTINENT TO 3578 02:21:17,360 --> 02:21:24,680 EMPLOYEE TRAINING WHICH COULD 3579 02:21:24,680 --> 02:21:25,560 PREVENT UNINTENDED DUPLICATION 3580 02:21:25,560 --> 02:21:28,080 AND DON'T IMPROVE METHODS OF 3581 02:21:28,080 --> 02:21:29,160 EXPERIMENTATION WHICH COULD 3582 02:21:29,160 --> 02:21:33,200 REDUCE OR REPLACE ANIMAL MUSE 3583 02:21:33,200 --> 02:21:35,040 AND MINIMIZE PAIN AND DISTRESS, 3584 02:21:35,040 --> 02:21:39,560 THE INTENT WAS TO HELP PEOPLE 3585 02:21:39,560 --> 02:21:41,880 FIND THIS TYPE OF INFORMATION. 3586 02:21:41,880 --> 02:21:47,840 MAIN STAKEHOLDERS WORK IN THE 3587 02:21:47,840 --> 02:21:52,160 ANIMAL RESEARCH SPACE. 3588 02:21:52,160 --> 02:21:52,680 P.I.s, LIBRARIANS, ANYONE 3589 02:21:52,680 --> 02:22:00,800 LOOKING FOR THIS LITERATURE. 3590 02:22:00,800 --> 02:22:02,440 WE PUT ON WORKSHOPS AND 3591 02:22:02,440 --> 02:22:04,720 TRAINING, IT'S INTERESTING THAT 3592 02:22:04,720 --> 02:22:06,160 THE ANIMAL WELFARE ACT 3593 02:22:06,160 --> 02:22:07,760 REGULATIONS SAY EMPLOYEES HAVE 3594 02:22:07,760 --> 02:22:08,640 TO RECEIVE TRAINING IN THE 3595 02:22:08,640 --> 02:22:10,520 FOLLOWING FIVE AREAS ON THE 3596 02:22:10,520 --> 02:22:11,000 SLIDE. 3597 02:22:11,000 --> 02:22:14,240 AND THE FIFTH AREA EVEN SAYS 3598 02:22:14,240 --> 02:22:20,560 UTILIZATION OF SERVICES SUCH AS 3599 02:22:20,560 --> 02:22:21,680 NATIONAL AGRICULTURAL LIBRARY, 3600 02:22:21,680 --> 02:22:26,400 AWIC, TO HELP YOU FIND 3601 02:22:26,400 --> 02:22:27,800 INFORMATION, ALTERNATIVES, 3602 02:22:27,800 --> 02:22:30,560 PREVENTION OF UNNECESSARY 3603 02:22:30,560 --> 02:22:31,240 DUPLICATION OF ANIMAL RESEARCH, 3604 02:22:31,240 --> 02:22:35,040 AND A TENTH OF THE REGULATIONS 3605 02:22:35,040 --> 02:22:41,040 OF THE ANIMAL WELFARE ACT. 3606 02:22:41,040 --> 02:22:44,960 NOW I'M GOING OVER PRODUCTS AND 3607 02:22:44,960 --> 02:22:46,880 SERVICES AVAILABLE TO YOU. 3608 02:22:46,880 --> 02:22:48,920 YOU MAY BE FAMILIAR WITH THE 3609 02:22:48,920 --> 02:22:49,360 WEBSITE. 3610 02:22:49,360 --> 02:22:51,680 WE DID GO OVER A HUGE REVAMP IN 3611 02:22:51,680 --> 02:22:55,320 THE LAST YEAR, MADE THE WEBSITE 3612 02:22:55,320 --> 02:22:59,280 MORE MODERN AND USER FRIENDLY, 3613 02:22:59,280 --> 02:23:05,360 MORE CONDENSED, MORE 3614 02:23:05,360 --> 02:23:05,840 AESTHETICALLY PLEASING. 3615 02:23:05,840 --> 02:23:08,520 A LOT OF WHAT YOU CAN FIND HAS 3616 02:23:08,520 --> 02:23:11,480 TO DO WITH THREE Rs 3617 02:23:11,480 --> 02:23:13,800 ALTERNATIVES, NAMs, WE HAVE 3618 02:23:13,800 --> 02:23:14,760 INFORMATION ON ANIMAL WELFARE 3619 02:23:14,760 --> 02:23:17,240 ACT AND FEDERAL LAWS GOVERNING 3620 02:23:17,240 --> 02:23:19,720 ANIMAL WELFARE, INSTRUCTIONS ON 3621 02:23:19,720 --> 02:23:22,200 HOW TO CONDUCT A LITERATURE 3622 02:23:22,200 --> 02:23:28,680 SEARCH FOR NAMs AND ANIMAL USE 3623 02:23:28,680 --> 02:23:29,760 ALTERNATIVES AND ALSO 3624 02:23:29,760 --> 02:23:31,600 BIBLIOGRAPHIES ON ANIMAL 3625 02:23:31,600 --> 02:23:33,040 RESEARCH TOPICS, EASIER FOR USER 3626 02:23:33,040 --> 02:23:35,000 TO FIND THAT INFORMATION VERSUS 3627 02:23:35,000 --> 02:23:37,080 SEARCHING ON YOUR OWN. 3628 02:23:37,080 --> 02:23:38,720 WE HAVE COMPILED BIBLIOGRAPHIES 3629 02:23:38,720 --> 02:23:44,760 WE KEEP UP TO DATE ANNUALLY. 3630 02:23:44,760 --> 02:23:55,160 ONE SPECIFIC WEB PAGE IS 3631 02:23:55,760 --> 02:23:56,760 ECO-TOXICITY PAGE, WHEN THEY 3632 02:23:56,760 --> 02:24:07,280 WERE WRITING CURRENT NEEDS OF 3633 02:24:13,920 --> 02:24:17,360 ECOTOXICITY, SO WE CONDUCTED A 3634 02:24:17,360 --> 02:24:20,880 SEARCH ON THE NAMs AND FROM 3635 02:24:20,880 --> 02:24:22,480 2010 TO 2022, UP TO DATE AND WE 3636 02:24:22,480 --> 02:24:24,560 PLAN TO UPDATE THIS YEAR AS 3637 02:24:24,560 --> 02:24:32,200 WELL, AND MADE IT PUBLICLY 3638 02:24:32,200 --> 02:24:33,560 AVAILABLE ON OUR WEBSITE. 3639 02:24:33,560 --> 02:24:34,880 IT'S A GREAT RESOURCE IF YOU'RE 3640 02:24:34,880 --> 02:24:37,040 TRYING TO FIND NAMs IN THIS 3641 02:24:37,040 --> 02:24:37,360 AREA. 3642 02:24:37,360 --> 02:24:47,840 MORE ON THIS PAGE THOUGH, WOE 3643 02:24:48,680 --> 02:24:50,960 HAVE CANNED LITERATURE SEARCHES 3644 02:24:50,960 --> 02:24:54,480 WHICH MEANS WE PRE-DEVELOPED 3645 02:24:54,480 --> 02:24:57,080 SEARCH STRING ON ECOTOXICITY 3646 02:24:57,080 --> 02:25:00,800 LITERATURE, IF YOU CLICK IT WILL 3647 02:25:00,800 --> 02:25:02,960 TAKE YOU TO THE MOST UPDATED 3648 02:25:02,960 --> 02:25:03,880 LITERATURE, WE MAKE THAT 3649 02:25:03,880 --> 02:25:11,000 AVAILABLE AND ALSO HAVE 3650 02:25:11,000 --> 02:25:17,440 DIFFERENT ECOTOXICITY TOOLS AND 3651 02:25:17,440 --> 02:25:24,000 TRAININGS IN THAT AREA. 3652 02:25:24,000 --> 02:25:25,080 THIS PROVIDES STEP-BY-STEP 3653 02:25:25,080 --> 02:25:26,160 INSTRUCTIONS FOR THE SEARCH, THE 3654 02:25:26,160 --> 02:25:28,160 MAIN PURPOSE OF THE PAGE BUT WE 3655 02:25:28,160 --> 02:25:34,920 ALSO PROVIDE OTHER TIPS AND 3656 02:25:34,920 --> 02:25:37,240 TRICKS, EXAMPLES, SYNTAX CHEAT 3657 02:25:37,240 --> 02:25:38,320 SHEETS AVAILABLE WHEN CONDUCTING 3658 02:25:38,320 --> 02:25:40,640 A SEARCH AND NEED TO KNOW WHICH 3659 02:25:40,640 --> 02:25:42,480 SYNTAX TO USE, DIFFERENT 3660 02:25:42,480 --> 02:25:43,800 PRACTICE WORKSHEETS, RESEARCH 3661 02:25:43,800 --> 02:25:46,760 PLANNING AND PUBLISHING GUYED 3662 02:25:46,760 --> 02:25:52,760 LINES SUCH AS ARRIVE, AND 3663 02:25:52,760 --> 02:25:53,760 FREQUENTLY ASKED QUESTIONS. 3664 02:25:53,760 --> 02:25:56,240 YOU CAN REACH OUT TO AWIC IF YOU 3665 02:25:56,240 --> 02:25:56,840 NEED HELP. 3666 02:25:56,840 --> 02:26:02,280 SOMETHING THAT YOU ALL MIGHT BE 3667 02:26:02,280 --> 02:26:12,840 FAMILIAR WITH, THE DATABASE THAT 3668 02:26:12,840 --> 02:26:14,160 IS MADE PUBLICLY AVAILABLE, 3669 02:26:14,160 --> 02:26:15,200 BIOMEDICAL SCIENCE, AGRICULTURE, 3670 02:26:15,200 --> 02:26:20,360 ANIMAL USE ALTERNATIVES. 3671 02:26:20,360 --> 02:26:27,240 YOU MAY BE FAMILIAR WITH 3672 02:26:27,240 --> 02:26:30,440 AGRICOLA, YOU CAN SEARCH PUBLIC 3673 02:26:30,440 --> 02:26:33,240 AG, DIGITAL COLLECTIONS IN ONE 3674 02:26:33,240 --> 02:26:35,920 PLATFORM, AND IT'S A LOT LESS 3675 02:26:35,920 --> 02:26:37,480 CLUNKY, USER FRIENDLY, IN 3676 02:26:37,480 --> 02:26:42,280 GENERAL MORE ADVANCED SEARCH AND 3677 02:26:42,280 --> 02:26:42,600 CAPABILITIES. 3678 02:26:42,600 --> 02:26:44,040 WHEN YOU'RE SEARCHING THE NEW 3679 02:26:44,040 --> 02:26:48,120 SEARCH INTERFACE YOU'LL LOOK AT 3680 02:26:48,120 --> 02:26:49,960 OUR JOURNAL ARTICLES, BOOKS, 3681 02:26:49,960 --> 02:26:51,920 DISSERTATIONS, CONFERENCE 3682 02:26:51,920 --> 02:26:54,360 PROCEEDINGS, A LOT OF MATERIAL 3683 02:26:54,360 --> 02:26:57,840 YOU'LL GET FROM NAL WILL BE 3684 02:26:57,840 --> 02:26:59,040 UNIQUE COMPARED TO WHERE YOU 3685 02:26:59,040 --> 02:27:01,600 WOULD FIND ELSEWHERE. 3686 02:27:01,600 --> 02:27:03,360 ANOTHER SERVICE WE OFFER IS OUR 3687 02:27:03,360 --> 02:27:05,200 MEETING REQUIREMENTS OF THE 3688 02:27:05,200 --> 02:27:06,400 ANIMAL WELFARE ACT WORKSHOP. 3689 02:27:06,400 --> 02:27:09,240 WE OFFER THIS THREE TIMES A YEAR 3690 02:27:09,240 --> 02:27:11,760 IN MARCH, MAY, OCTOBER, IT IS 3691 02:27:11,760 --> 02:27:14,280 FREE TO ATTEND, AND THIS FALL IT 3692 02:27:14,280 --> 02:27:16,360 WILL BE VIRTUAL ACROSS TWO HALF 3693 02:27:16,360 --> 02:27:16,840 DAYS. 3694 02:27:16,840 --> 02:27:18,760 THE MAIN PURPOSE OF THIS 3695 02:27:18,760 --> 02:27:20,520 WORKSHOP IS TO PROVIDE 3696 02:27:20,520 --> 02:27:22,160 INFORMATION ON THE ANIMAL 3697 02:27:22,160 --> 02:27:24,920 WELFARE ACT, REGULATIONS P.I.s 3698 02:27:24,920 --> 02:27:27,800 HAVE TO FOLLOW AND WHY, NEW AND 3699 02:27:27,800 --> 02:27:30,960 UPDATED ANIMAL USE ALTERNATIVE 3700 02:27:30,960 --> 02:27:33,480 EXAMPLES AND NAMs, AND BULK OF 3701 02:27:33,480 --> 02:27:37,280 THE PRESENTATION IS TEACHING 3702 02:27:37,280 --> 02:27:40,160 PATRONS HOW TO SEARCH FOR ANIMAL 3703 02:27:40,160 --> 02:27:42,680 USE ALTERNATIVES IN THE 3704 02:27:42,680 --> 02:27:44,200 LITERATURE, A SYSTEMATIC 3705 02:27:44,200 --> 02:27:45,200 APPROACH VERSUS KEY WORDS TO 3706 02:27:45,200 --> 02:27:53,840 PLUG IN TO GOOGLE OR GOOGLE 3707 02:27:53,840 --> 02:27:54,400 SCHOLAR. 3708 02:27:54,400 --> 02:27:56,560 IF YOU'RE NOT ABLE TO ATTEND A 3709 02:27:56,560 --> 02:27:58,960 LIVE WORKSHOP WE RECOMMEND, WE 3710 02:27:58,960 --> 02:28:01,480 DID LAUNCH OUR WORKSHOP ONLINE 3711 02:28:01,480 --> 02:28:03,000 IN A FREE ON-DEMAND AND 3712 02:28:03,000 --> 02:28:03,480 SELF-PACED FORMAT. 3713 02:28:03,480 --> 02:28:05,800 IF YOU CAN'T MAKE ONE OF THE 3714 02:28:05,800 --> 02:28:07,520 STAGNANT DATES THROUGHOUT THE 3715 02:28:07,520 --> 02:28:08,960 YEARS, ACCESS OUR ONLINE 3716 02:28:08,960 --> 02:28:10,360 WORKSHOP AT ANY TIME AND TAKE IT 3717 02:28:10,360 --> 02:28:12,240 AT YOUR OWN PACE. 3718 02:28:12,240 --> 02:28:14,520 THE DOWN SIDE IS YOU WON'T HAVE 3719 02:28:14,520 --> 02:28:15,960 THOSE LIVE INTERACTIONS AND 3720 02:28:15,960 --> 02:28:18,560 DISCUSSIONS AND ENGAGEMENTS THAT 3721 02:28:18,560 --> 02:28:27,000 YOU MIGHT MIGHT WITH WORKSHOPS. 3722 02:28:27,000 --> 02:28:28,120 AND CUSTOMIZABLE TRAININGS, WE 3723 02:28:28,120 --> 02:28:29,320 OFFER ON REQUEST. 3724 02:28:29,320 --> 02:28:31,160 IF AN AGENCY OR INSTITUTION 3725 02:28:31,160 --> 02:28:33,400 SAYS, HEY, WE DON'T NEED ANY 3726 02:28:33,400 --> 02:28:34,880 REFRESHER ON THE REGULATIONS OR 3727 02:28:34,880 --> 02:28:38,200 ACT BUT WE NEED HELP FINDING 3728 02:28:38,200 --> 02:28:45,520 LITERATURE ON THIS TOPIC, WE CAN 3729 02:28:45,520 --> 02:28:47,000 CONDENSE OR CREATE A SPECIFIC 3730 02:28:47,000 --> 02:28:48,280 PRESENTATION BASED ON NEEDS OF 3731 02:28:48,280 --> 02:28:50,120 FACILITY OR INSTITUTION. 3732 02:28:50,120 --> 02:28:52,720 TOPICS ARE FLEXIBLE AND DEPEND 3733 02:28:52,720 --> 02:28:54,600 ON WHAT FACILITY OR AGENCY IS 3734 02:28:54,600 --> 02:28:56,680 INTERESTED IN. 3735 02:28:56,680 --> 02:28:58,520 AND THEY CAN BE AS LONG OR SHORT 3736 02:28:58,520 --> 02:29:00,120 AS THEY WANT. 3737 02:29:00,120 --> 02:29:05,120 TIMING AND TOPICS ARE FLEXIBLE. 3738 02:29:05,120 --> 02:29:07,600 WHILE WE TEACH PEOPLE HOW TO 3739 02:29:07,600 --> 02:29:09,160 CONDUCT LITERATURE SEARCHES, WE 3740 02:29:09,160 --> 02:29:11,680 DO THEM ON REQUEST SO IF YOU ARE 3741 02:29:11,680 --> 02:29:12,440 HAVING TROUBLE FINDING 3742 02:29:12,440 --> 02:29:14,200 INFORMATION ON A SPECIFIC NAM OR 3743 02:29:14,200 --> 02:29:15,720 ANIMAL USE ALTERNATIVE YOU CAN 3744 02:29:15,720 --> 02:29:18,880 E-MAIL US AND WE CAN HELP YOU 3745 02:29:18,880 --> 02:29:22,560 FIND THAT INFORMATION. 3746 02:29:22,560 --> 02:29:24,160 FOR MORE TRADITIONAL PROTOCOLS, 3747 02:29:24,160 --> 02:29:25,880 P.I.s MIGHT NEED HELP 3748 02:29:25,880 --> 02:29:27,560 CONDUCTING THE SEARCH AND SO IF 3749 02:29:27,560 --> 02:29:28,680 THEY SEND THEIR PROTOCOL IF THEY 3750 02:29:28,680 --> 02:29:31,000 ARE ABLE TO WE CAN CONDUCT THAT 3751 02:29:31,000 --> 02:29:33,280 SEARCH FOR THEM AND IDENTIFY 3752 02:29:33,280 --> 02:29:35,240 ALTERNATIVES IN THAT RESEARCH 3753 02:29:35,240 --> 02:29:35,440 SPACE. 3754 02:29:35,440 --> 02:29:39,160 AND THEN THIS LINK IS TAKING YOU 3755 02:29:39,160 --> 02:29:41,360 TO OUR LITERATURE SEARCH REQUEST 3756 02:29:41,360 --> 02:29:41,520 FOR. 3757 02:29:41,520 --> 02:29:43,640 IN GENERAL IF YOU HAVE QUESTIONS 3758 02:29:43,640 --> 02:29:46,520 ON NAMs OR ANIMAL USE 3759 02:29:46,520 --> 02:29:48,040 ALTERNATIVES FEEL FREE TO E-MAIL 3760 02:29:48,040 --> 02:29:48,440 US. 3761 02:29:48,440 --> 02:29:49,920 IF WE CAN'T TELL YOU THE EXACT 3762 02:29:49,920 --> 02:29:51,440 ANSWER WE CAN POINT YOU IN THE 3763 02:29:51,440 --> 02:29:56,360 DIRECTION OF SOMEONE WHO CAN. 3764 02:29:56,360 --> 02:29:59,200 AND THEN LASTLY, OUR AWIC 3765 02:29:59,200 --> 02:30:03,800 NEWSLETTER WE SEND THESE OUT 3766 02:30:03,800 --> 02:30:07,560 ONCE A MONTH COVERING NEW THREE 3767 02:30:07,560 --> 02:30:11,800 Rs RESEARCH OR NAMs, 3768 02:30:11,800 --> 02:30:13,200 TIPS, ORGANIZE CONFERENCE AND 3769 02:30:13,200 --> 02:30:14,640 TRAININGS, NEW UPDATES COMING 3770 02:30:14,640 --> 02:30:19,360 OUT FROM THE ANIMAL WELFARE ACT, 3771 02:30:19,360 --> 02:30:19,800 OR AWIC. 3772 02:30:19,800 --> 02:30:25,040 IT'S A GOOD WAY TO STAY UP TO 3773 02:30:25,040 --> 02:30:25,720 DATE. 3774 02:30:25,720 --> 02:30:28,880 AND WE HAVE A DIGITAL 3775 02:30:28,880 --> 02:30:30,000 COLLECTION, ESSENTIALLY THIS 3776 02:30:30,000 --> 02:30:31,640 HOLDS FULL TEXT SEARCHABLE 3777 02:30:31,640 --> 02:30:35,920 REGULATORY AND LEGISLATIVE 3778 02:30:35,920 --> 02:30:37,200 DOCUMENTS SO IF YOU WANT TO FIND 3779 02:30:37,200 --> 02:30:39,720 A SPECIFIC HEARING OR BILL OR 3780 02:30:39,720 --> 02:30:40,920 PROPOSED RULE OR LAW, YOU'LL 3781 02:30:40,920 --> 02:30:42,240 FIND IT IN THIS DIGITAL 3782 02:30:42,240 --> 02:30:42,640 COLLECTION. 3783 02:30:42,640 --> 02:30:44,560 IT'S GOOD FOR PEOPLE WHO WANT TO 3784 02:30:44,560 --> 02:30:46,720 KNOW WHY SOMETHING WAS PASSED, 3785 02:30:46,720 --> 02:30:48,800 WHAT WAS THE REAL INTENT, 3786 02:30:48,800 --> 02:30:50,360 CONVERSATIONS THAT LED TO IT, 3787 02:30:50,360 --> 02:30:52,520 THAT'S THE KIND OF INFORMATION 3788 02:30:52,520 --> 02:30:53,280 THAT YOU'LL FIND HERE. 3789 02:30:53,280 --> 02:30:57,080 IF YOU WANT A MORE BROAD 3790 02:30:57,080 --> 02:31:00,480 OVERVIEW THERE'S AN INTERACTIVE 3791 02:31:00,480 --> 02:31:06,200 TIMELINE ON OUR HOME PAGE, SO 3792 02:31:06,200 --> 02:31:07,520 THAT WILL TAKE YOU THROUGH THE 3793 02:31:07,520 --> 02:31:09,360 AMENDMENTS OF THE ANIMAL WELFARE 3794 02:31:09,360 --> 02:31:11,680 ACT OVER TIME SO GIVES AN IDEA 3795 02:31:11,680 --> 02:31:14,200 HOW THE ACT SHAPED AND WAS 3796 02:31:14,200 --> 02:31:17,480 EVOLVED. 3797 02:31:17,480 --> 02:31:21,000 I WANTED TO GO OVER TWO PROJECTS 3798 02:31:21,000 --> 02:31:22,400 THAT AWIC IS WORKING ON OF 3799 02:31:22,400 --> 02:31:23,840 INTEREST TO YOU. 3800 02:31:23,840 --> 02:31:32,040 FIRST IS SOMEWHAT SIMILAR TO A 3801 02:31:32,040 --> 02:31:38,480 PROJECT THAT NICOLE PRESENTED 3802 02:31:38,480 --> 02:31:39,040 ON. 3803 02:31:39,040 --> 02:31:41,000 TYPICALLY, P.I.s WHEN WRITING 3804 02:31:41,000 --> 02:31:44,280 PAPERS MIGHT NOT BE EXPLICITLY 3805 02:31:44,280 --> 02:31:47,800 USING THE TERMS, NEW APPROACH 3806 02:31:47,800 --> 02:31:49,120 METHODOLOGY, NAMs, THREE Rs, 3807 02:31:49,120 --> 02:31:53,240 THOSE TERMS THAT THE AVERAGE 3808 02:31:53,240 --> 02:31:54,480 LITERATURE SEARCHER MIGHT BE 3809 02:31:54,480 --> 02:31:54,800 PLUGGING IN. 3810 02:31:54,800 --> 02:31:57,520 THEY WILL USE MORE SPECIFIC AN 3811 02:31:57,520 --> 02:31:59,160 RELEVANT TERMINOLOGY TO THEIR 3812 02:31:59,160 --> 02:31:59,400 RESEARCH. 3813 02:31:59,400 --> 02:32:07,040 WHAT WE'RE TRYING TO DO IS 3814 02:32:07,040 --> 02:32:15,480 UPDATE THE THESAURUS, AND ALSO 3815 02:32:15,480 --> 02:32:18,080 IMPROVING CONTROLLED VOCABULARY 3816 02:32:18,080 --> 02:32:22,720 AND TAXONOMY TO IMPROVE CITATIN 3817 02:32:22,720 --> 02:32:23,240 INDEXING. 3818 02:32:23,240 --> 02:32:26,320 WE'RE DOING USER TESTING TRYING 3819 02:32:26,320 --> 02:32:29,240 TO TRAIN ARTIFICIAL INTELLIGENCE 3820 02:32:29,240 --> 02:32:32,400 TECHNOLOGY TO RECOGNIZE NAMs 3821 02:32:32,400 --> 02:32:33,080 CITATIONS WITHOUT MAYBE HAVING 3822 02:32:33,080 --> 02:32:34,640 THOSE TERMS THAT WE THINK OF 3823 02:32:34,640 --> 02:32:38,120 WHEN WE THINK OF NAMs AND 3824 02:32:38,120 --> 02:32:39,680 ANIMAL USE ALTERNATIVES, 3825 02:32:39,680 --> 02:32:41,920 TEACHING A.I. TECHNOLOGY CONTEXT 3826 02:32:41,920 --> 02:32:44,160 CLUES TO FIND THESE CITATIONS 3827 02:32:44,160 --> 02:32:45,680 EVEN IF NOT EXPLICITLY TALKED 3828 02:32:45,680 --> 02:32:47,000 ABOUT IN THAT WAY. 3829 02:32:47,000 --> 02:32:50,120 WE'RE DOING SOME USER TESTING 3830 02:32:50,120 --> 02:32:55,680 THIS SUMMER SO HOPEFULLY WE'LL 3831 02:32:55,680 --> 02:32:58,600 HAVE NEW UPDATE SOON. 3832 02:32:58,600 --> 02:33:01,160 LAST INITIATIVE IS OUR 3 Rs 3833 02:33:01,160 --> 02:33:02,000 SEARCH STRINGS, YOU AREN'T 3834 02:33:02,000 --> 02:33:05,960 FAMILIAR WITH WHAT A HEDGE IS 3835 02:33:05,960 --> 02:33:09,640 BUT A SEARCH HEDGE IS A 3836 02:33:09,640 --> 02:33:10,640 PRE-DETERMINED OR PRE-DEVELOPED 3837 02:33:10,640 --> 02:33:13,080 SEARCH STRING SO IN THEORY THE 3838 02:33:13,080 --> 02:33:15,600 LIBRARIANS AND SUBJECT MATTER 3839 02:33:15,600 --> 02:33:18,080 EXPERTS ARE DEVELOPING TECHNICAL 3840 02:33:18,080 --> 02:33:19,000 BUT COMPREHENSIVE SEARCH STRINGS 3841 02:33:19,000 --> 02:33:22,040 SO THE P.I. CAN COPY AND PASTE 3842 02:33:22,040 --> 02:33:23,040 WHATEVER SEARCH STRING IS 3843 02:33:23,040 --> 02:33:24,120 RELEVANT TO THEIR RESEARCH AND 3844 02:33:24,120 --> 02:33:29,520 PLUG IT INTO THE DATA DATABASED 3845 02:33:29,520 --> 02:33:31,160 TWEAK BUT AT LEAST GIVES THEM A 3846 02:33:31,160 --> 02:33:32,680 STARTING POINT. 3847 02:33:32,680 --> 02:33:39,560 FOR EXAMPLE THIS IS BASIC, A 3848 02:33:39,560 --> 02:33:40,880 SIMPLE EXAMPLE ON RATS. 3849 02:33:40,880 --> 02:33:42,440 YOU WOULDN'T JUST INCLUDE THE 3850 02:33:42,440 --> 02:33:43,840 TERM RAT OR RATS. 3851 02:33:43,840 --> 02:33:45,920 YOU WOULD WAND TO INCLUDE ALL 3852 02:33:45,920 --> 02:33:47,320 THESE ADDITIONAL TERMS TO MAKE 3853 02:33:47,320 --> 02:33:49,280 SURE YOU'RE ACCOUNTING FOR ALL 3854 02:33:49,280 --> 02:33:52,280 THE DIFFERENT WAYS P.I.s MIGHT 3855 02:33:52,280 --> 02:33:54,000 REFER, SCIENTIFIC NAME, LATIN 3856 02:33:54,000 --> 02:33:56,720 NAME, SPECIES STRAIN, THOSE 3857 02:33:56,720 --> 02:33:58,600 KINDS OF SPECIFIC DETAILS. 3858 02:33:58,600 --> 02:34:00,480 THERE SHOULD BE, YEAH, ANOTHER 3859 02:34:00,480 --> 02:34:00,880 ONE. 3860 02:34:00,880 --> 02:34:02,640 THE SECOND ONE IS ON HOUSING. 3861 02:34:02,640 --> 02:34:04,840 IF YOU'RE LOOKING FOR 3862 02:34:04,840 --> 02:34:06,400 REFINEMENTS IN YOUR HOUSING 3863 02:34:06,400 --> 02:34:07,520 ENVIRONMENT FOR YOUR ANIMALS, 3864 02:34:07,520 --> 02:34:09,320 YOU MIGHT USE THIS KIND OF 3865 02:34:09,320 --> 02:34:12,160 SEARCH STRING WHICH ISN'T JUST 3866 02:34:12,160 --> 02:34:15,040 USING THE TERMS ENCLOSURE, CAGE, 3867 02:34:15,040 --> 02:34:15,240 HOUSING. 3868 02:34:15,240 --> 02:34:17,520 IT'S GETTING AT SOCIAL HOUSING, 3869 02:34:17,520 --> 02:34:20,360 GROUP HOUSING, PAIR HOUSING, 3870 02:34:20,360 --> 02:34:20,920 BEHAVIORAL MANAGEMENT, THOSE 3871 02:34:20,920 --> 02:34:23,680 TERMS IN THE PAPERS THAT YOU'RE 3872 02:34:23,680 --> 02:34:24,840 LOOKING FOR THAT MIGHT NOT REFER 3873 02:34:24,840 --> 02:34:32,400 TO IT AS ALTERNATIVE OR 3874 02:34:32,400 --> 02:34:33,400 REFINEMENT. 3875 02:34:33,400 --> 02:34:34,360 WE'RE STILL TRYING TO VALIDATE 3876 02:34:34,360 --> 02:34:37,320 AND DO SOME USER TESTING SO I 3877 02:34:37,320 --> 02:34:40,160 DIDN'T WANT TO SHOW SOME WITHOUT 3878 02:34:40,160 --> 02:34:41,600 BEING, QUOTE, PERFECT. 3879 02:34:41,600 --> 02:34:43,120 WE'VE MADE SOME PUBLICLY 3880 02:34:43,120 --> 02:34:44,760 AVAILABLE ON THE LINK ON THE 3881 02:34:44,760 --> 02:34:44,960 SLIDE. 3882 02:34:44,960 --> 02:34:47,600 AGAIN, THEY WILL FOCUS MORE ON 3883 02:34:47,600 --> 02:34:49,680 GENERAL 3 R SPACE AND ANIMAL 3884 02:34:49,680 --> 02:34:53,720 SPECIES SPRING BUT -- STRING BT 3885 02:34:53,720 --> 02:34:55,920 WE'RE COMING OUT WITH NAMs 3886 02:34:55,920 --> 02:34:57,960 STRINGS HOPEFULLY AVAILABLE NEXT 3887 02:34:57,960 --> 02:34:58,160 MONTH. 3888 02:34:58,160 --> 02:34:59,640 AND THEN THAT'S ALL I HAVE TO 3889 02:34:59,640 --> 02:35:05,200 SHARE TODAY BUT FEEL FREE TO 3890 02:35:05,200 --> 02:35:07,160 REACH OUR CONTACT INFORMATION TO 3891 02:35:07,160 --> 02:35:14,760 REACH OUT FOR COMMENTS, 3892 02:35:14,760 --> 02:35:16,680 QUESTIONS, CONCERNS. 3893 02:35:16,680 --> 02:35:17,640 THANKS. 3894 02:35:17,640 --> 02:35:17,920 [APPLAUSE] 3895 02:35:17,920 --> 02:35:18,800 >>GREAT. 3896 02:35:18,800 --> 02:35:21,440 THANKS, JESSIE. 3897 02:35:21,440 --> 02:35:24,360 DO WE HAVE ANY QUESTIONS ONLINE 3898 02:35:24,360 --> 02:35:25,440 OR IN THE ROOM? 3899 02:35:25,440 --> 02:35:28,760 >> QUICK COMMENT AND A 3900 02:35:28,760 --> 02:35:29,520 QUESTION. 3901 02:35:29,520 --> 02:35:35,000 THAT IN DOI WE USE CUSTOMIZABLE 3902 02:35:35,000 --> 02:35:35,880 TRAINING. 3903 02:35:35,880 --> 02:35:36,160 JESSICA LEE. 3904 02:35:36,160 --> 02:35:42,440 YEAH, BARNETT AND I WORKED WITH 3905 02:35:42,440 --> 02:35:43,520 JESSIE TO CREATE CUSTOMIZABLE 3906 02:35:43,520 --> 02:35:45,080 TRAINING, IT WAS EXTREMELY 3907 02:35:45,080 --> 02:35:48,160 HELPFUL, JUST A PLUG FOR THE 3908 02:35:48,160 --> 02:35:48,800 USEFULNESS OF THAT. 3909 02:35:48,800 --> 02:35:52,960 THAT WAS PART OF OUR METRICS 3910 02:35:52,960 --> 02:35:54,400 THAT WE'RE DOING. 3911 02:35:54,400 --> 02:35:55,440 YOU SAID THERE'S UPDATED 3912 02:35:55,440 --> 02:35:57,320 TRAINING FOR THE MEETING THAT 3913 02:35:57,320 --> 02:36:00,280 ANIMAL WELFARE ACT, IS THAT 3914 02:36:00,280 --> 02:36:02,840 THROUGH AWIC AS OPPOSED TO THE 3915 02:36:02,840 --> 02:36:06,600 OSU TRAINING OR IS IT STILL THAT 3916 02:36:06,600 --> 02:36:07,000 OSU TRAINING? 3917 02:36:07,000 --> 02:36:10,320 >>IT'S ALWAYS BEEN THROUGH 3918 02:36:10,320 --> 02:36:10,720 AWIC. 3919 02:36:10,720 --> 02:36:12,640 WE CONTRACT WITH A UNIVERSITY, 3920 02:36:12,640 --> 02:36:15,080 BUT WENT THROUGH MAIN UPDATES 3921 02:36:15,080 --> 02:36:17,120 ABOUT A YEAR AND A HALF AGO AND 3922 02:36:17,120 --> 02:36:18,760 ANOTHER SET OF UPDATES TO MAKE 3923 02:36:18,760 --> 02:36:21,920 SURE THE CONTENT IS TRUE. 3924 02:36:21,920 --> 02:36:25,360 >> IN DOI WE HAD TO USE A 3925 02:36:25,360 --> 02:36:28,280 DIFFERENT E-MAIL. 3926 02:36:28,280 --> 02:36:32,600 THAT WAS WEIRD. 3927 02:36:32,600 --> 02:36:32,960 OKAY FANTASTIC. 3928 02:36:32,960 --> 02:36:35,440 THANK YOU. 3929 02:36:35,440 --> 02:36:37,160 >> PERFECT. 3930 02:36:37,160 --> 02:36:38,680 ANY QUESTIONS FROM ONLINE? 3931 02:36:38,680 --> 02:36:41,560 OKAY. 3932 02:36:41,560 --> 02:36:43,920 THANK YOU SO MUCH. 3933 02:36:43,920 --> 02:36:48,640 SO, LET ME STOP SHARING BECAUSE 3934 02:36:48,640 --> 02:36:53,440 OUR NEXT PRESENTER IS ONLINE. 3935 02:36:53,440 --> 02:36:57,200 DR. VALERIO FROM FDA CTP. 3936 02:36:57,200 --> 02:36:58,400 WE CAN SEE YOU. 3937 02:36:58,400 --> 02:37:06,840 >>GREAT. 3938 02:37:06,840 --> 02:37:17,200 I'LL SHARE MY SCREEN. 3939 02:37:29,640 --> 02:37:33,840 I'M LUIS VALERIO, CENTER FOR 3940 02:37:33,840 --> 02:37:38,840 TOBACCO PRODUCTS, I'LL REFER TO 3941 02:37:38,840 --> 02:37:40,840 THAT AS CTP, PROBABLY A NEW 3942 02:37:40,840 --> 02:37:42,040 ACRONYM FOR YOU. 3943 02:37:42,040 --> 02:37:44,880 DELIGHTED TO SPEAK TO HOW WE'RE 3944 02:37:44,880 --> 02:37:45,880 ADVANCING NEW APPROACH METHODS 3945 02:37:45,880 --> 02:37:49,040 IN SUPPORT OF OUR REGULATORY 3946 02:37:49,040 --> 02:37:52,120 REVIEW OF TOBACCO PRODUCTS IN 3947 02:37:52,120 --> 02:37:55,480 THE CONTEXT OF TOXICOLOGY. 3948 02:37:55,480 --> 02:37:56,680 SO, THIS PRESENTATION WILL 3949 02:37:56,680 --> 02:37:58,760 CONTAIN MY VIEWS AND OPINIONS 3950 02:37:58,760 --> 02:38:00,320 AND MAY NOT NECESSARILY REFLECT 3951 02:38:00,320 --> 02:38:01,520 THAT OF THE FDA. 3952 02:38:01,520 --> 02:38:04,600 IF I MENTION ANY COMMERCIAL 3953 02:38:04,600 --> 02:38:08,520 PRODUCTS, THERE'S NO INTENDED 3954 02:38:08,520 --> 02:38:09,640 ENDORSEMENT OR IMPLIED. 3955 02:38:09,640 --> 02:38:13,560 BASICALLY, I WANT TO TALK ABOUT 3956 02:38:13,560 --> 02:38:15,080 OBVIOUSLY TOBACCO PRODUCTS, I 3957 02:38:15,080 --> 02:38:18,160 THINK IT'S IMPORTANT FOR YOU TO 3958 02:38:18,160 --> 02:38:21,000 GET A GRASP BEFORE WE GET INTO 3959 02:38:21,000 --> 02:38:23,840 THE SPECIFIC NAMs OF OUR 3960 02:38:23,840 --> 02:38:26,120 REGULATORY AUTHORITY, KIND OF 3961 02:38:26,120 --> 02:38:29,640 PRODUCTS, AND THEN CONTINUALLY 3962 02:38:29,640 --> 02:38:31,080 THROUGHOUT THE SHORT TALK I'LL 3963 02:38:31,080 --> 02:38:33,480 BE DRIVING AT OUR LONG-TERM 3964 02:38:33,480 --> 02:38:35,200 COMMITMENT AND INTEREST TO NEW 3965 02:38:35,200 --> 02:38:36,160 APPROACH METHODS. 3966 02:38:36,160 --> 02:38:38,800 BUT IF THERE'S ANYTHING THAT YOU 3967 02:38:38,800 --> 02:38:41,480 TAKE AWAY FROM THIS I'D LIKE YOU 3968 02:38:41,480 --> 02:38:46,720 TO -- LIKE A TAKEHOME MESSAGE 3969 02:38:46,720 --> 02:38:49,040 PROGRAMMATIC APPROACH TO NAMs, 3970 02:38:49,040 --> 02:38:51,320 AGAIN, THAT'S TO SUPPORT -- I'M 3971 02:38:51,320 --> 02:38:52,960 FROM DIVISION OF NON-CLINICAL 3972 02:38:52,960 --> 02:38:57,000 SCIENCE, A DIVISION OF 3973 02:38:57,000 --> 02:38:58,960 TOXICOLOGISTS, AND HOW WE 3974 02:38:58,960 --> 02:38:59,560 SUPPORT REGULATORY TOXICOLOGY 3975 02:38:59,560 --> 02:39:00,560 REVIEWS. 3976 02:39:00,560 --> 02:39:03,800 I KNOW THERE'S BEEN A LOT OF -- 3977 02:39:03,800 --> 02:39:05,440 THERE'S GREAT METHODS AND 3978 02:39:05,440 --> 02:39:09,080 EVERYBODY WANTS TO KNOW HOW CAN 3979 02:39:09,080 --> 02:39:12,600 WE GET THESE THINGS REGULATORY 3980 02:39:12,600 --> 02:39:17,160 ACCEPTED, AND SO I'LL COVER SOME 3981 02:39:17,160 --> 02:39:18,600 PROGRAMMATIC APPROACH, WHICH 3982 02:39:18,600 --> 02:39:20,720 THAT WAS TOUCHED UPON BY MY 3983 02:39:20,720 --> 02:39:23,880 COLLEAGUE AT THE V.A. EARLIER 3984 02:39:23,880 --> 02:39:26,120 TODAY, GEORGE LATHROP, GREAT TO 3985 02:39:26,120 --> 02:39:27,760 HEAR. 3986 02:39:27,760 --> 02:39:30,080 BUT I'LL COVER SOME ACTIVITIES. 3987 02:39:30,080 --> 02:39:33,920 FIRST I WANT TO KIND OF PROVIDE 3988 02:39:33,920 --> 02:39:37,760 CONTEXT, OUR MISSION IS TO 3989 02:39:37,760 --> 02:39:38,360 PROTECT AMERICANS FROM 3990 02:39:38,360 --> 02:39:39,280 TOBACCO-RELATED DEATH AND 3991 02:39:39,280 --> 02:39:39,720 DISEASE. 3992 02:39:39,720 --> 02:39:43,120 THAT'S THROUGH REGULATION OF THE 3993 02:39:43,120 --> 02:39:43,560 PRODUCTS. 3994 02:39:43,560 --> 02:39:45,480 AND ESPECIALLY IMPORTANT IS 3995 02:39:45,480 --> 02:39:49,000 EDUCATING THE PUBLIC AND 3996 02:39:49,000 --> 02:39:51,000 PARTICULARLY OUR YOUTH, TO 3997 02:39:51,000 --> 02:39:57,560 PROTECT THEM FROM DANGERS THESE 3998 02:39:57,560 --> 02:40:03,560 PRODUCTS POSE. 3999 02:40:03,560 --> 02:40:07,080 WE DERIVE FROM TAKE CONTROL ACT 4000 02:40:07,080 --> 02:40:10,360 SIGNED IN 2009, AND GAVE FDA 4001 02:40:10,360 --> 02:40:13,840 BROAD AUTHORITY TO REGULATE 4002 02:40:13,840 --> 02:40:16,800 CIGARETTES, CIGARETTE TOBACCO, 4003 02:40:16,800 --> 02:40:20,000 SMOKELESS TOBACCO, ROLL-YOUR-OWN 4004 02:40:20,000 --> 02:40:20,440 TOBACCO. 4005 02:40:20,440 --> 02:40:21,640 LATER IN AUGUST 2016 THE 4006 02:40:21,640 --> 02:40:24,560 AUTHORITY WAS EXTENDED TO OTHER 4007 02:40:24,560 --> 02:40:26,200 TOBACCO PRODUCTS, INCLUDING 4008 02:40:26,200 --> 02:40:27,960 CIGARS, I'VE LISTED SOME HERE, 4009 02:40:27,960 --> 02:40:29,920 BUT THERE'S BEEN A LOT IN THE 4010 02:40:29,920 --> 02:40:34,400 NEWS AND DISCUSSION AND RESEARCH 4011 02:40:34,400 --> 02:40:38,480 ABOUT ELECTRONIC CIGARETTES, WE 4012 02:40:38,480 --> 02:40:42,520 CALL THESE ELECTRONIC NICOTINE 4013 02:40:42,520 --> 02:40:45,560 DELIVERY SYSTEMS. 4014 02:40:45,560 --> 02:40:48,840 CONGRESS PASSED A LAW JUST IN 4015 02:40:48,840 --> 02:40:50,720 APRIL 2022 THAT GAVE FDA 4016 02:40:50,720 --> 02:41:00,680 AUTHORITY TO REGULATE SYNTHETIC 4017 02:41:00,680 --> 02:41:01,880 NICOTINE, NON-TOBACCO-DERIVED 4018 02:41:01,880 --> 02:41:03,520 NICOTINE, R-ISOMER. 4019 02:41:03,520 --> 02:41:05,280 REGULATING ANYTHING THAT 4020 02:41:05,280 --> 02:41:07,240 CONTAINS NICOTINE EXCEPT FOR 4021 02:41:07,240 --> 02:41:10,520 THOSE PRODUCTS WITH THERAPEUTIC 4022 02:41:10,520 --> 02:41:12,360 PURPOSE OR FOOD OR OTHER CENTERS 4023 02:41:12,360 --> 02:41:15,760 WOULD REGULATE THOSE PRODUCTS. 4024 02:41:15,760 --> 02:41:19,480 SO, THAT GIVES A PICTURE, 4025 02:41:19,480 --> 02:41:20,280 IMPORTANT BACKDROP. 4026 02:41:20,280 --> 02:41:24,560 ALSO PROBABLY MAY NOT BE 4027 02:41:24,560 --> 02:41:27,040 FAMILIAR WITH BASICALLY THE KIND 4028 02:41:27,040 --> 02:41:28,800 OF PATHWAYS TO MARKET. 4029 02:41:28,800 --> 02:41:38,680 THERE ARE THREE FOR TOBACCO. 4030 02:41:38,680 --> 02:41:40,160 SE, EXEMPTION AND PMTA. 4031 02:41:40,160 --> 02:41:43,320 A LOT OF ELECTRONIC CIGARETTES 4032 02:41:43,320 --> 02:41:45,520 COME THROUGH THIS PATHWAY, 4033 02:41:45,520 --> 02:41:46,200 STATUTORY STANDARD IS 4034 02:41:46,200 --> 02:41:47,960 APPROPRIATE FOR PROTECTION OF 4035 02:41:47,960 --> 02:41:48,280 PUBLIC HEALTH. 4036 02:41:48,280 --> 02:41:51,000 WITH THAT WE NEED TO UNDERSTAND 4037 02:41:51,000 --> 02:41:54,400 HEALTH EFFECTS ON THE WHOLE 4038 02:41:54,400 --> 02:41:57,480 POPULATION SO THAT INCLUDES 4039 02:41:57,480 --> 02:41:59,880 RISK/BENEFIT BUT HOW THE PRODUCT 4040 02:41:59,880 --> 02:42:02,840 COULD IMPACT NON-USERS AS WELL 4041 02:42:02,840 --> 02:42:06,880 INCLUDING IF THERE'S A MARKETING 4042 02:42:06,880 --> 02:42:07,760 AUTHORIZATION ON ENVIRONMENTAL 4043 02:42:07,760 --> 02:42:11,120 ASSESSMENT, BUT THAT'S A 4044 02:42:11,120 --> 02:42:13,760 DIFFERENT REGULATION, NATIONAL 4045 02:42:13,760 --> 02:42:15,960 ENVIRONMENTAL POLICY ACT. 4046 02:42:15,960 --> 02:42:17,080 TOXOLOGICAL EFFECTS WHERE WE 4047 02:42:17,080 --> 02:42:20,120 FOCUS ON HERE WITH NAMs, THIS 4048 02:42:20,120 --> 02:42:26,960 GIVES YOU A PICTURE OF WHERE IN 4049 02:42:26,960 --> 02:42:27,800 OUR REGULATORY OVERSIGHT COULD 4050 02:42:27,800 --> 02:42:30,120 WE BE SEEING THAT. 4051 02:42:30,120 --> 02:42:32,320 I WOULD BE REMISS IF I DID NOT 4052 02:42:32,320 --> 02:42:33,840 TALK ABOUT THE FANTASTIC 4053 02:42:33,840 --> 02:42:35,040 COLLEAGUES IN OFFICE OF SCIENCE 4054 02:42:35,040 --> 02:42:37,560 AT THE CENTER FOR TOBACCO 4055 02:42:37,560 --> 02:42:40,520 PRODUCTS, AND THIS IS KIND OF A 4056 02:42:40,520 --> 02:42:42,840 SKETCH OF ALL THE DISCIPLINES 4057 02:42:42,840 --> 02:42:43,920 THAT COME TOGETHER WHEN THERE 4058 02:42:43,920 --> 02:42:46,920 IS, FOR EXAMPLE, A PMTA, AND IT 4059 02:42:46,920 --> 02:42:51,800 REALLY TAKES A LOT OF TEAM WORK, 4060 02:42:51,800 --> 02:42:53,680 COORDINATION, AND TOXICOLOGY IS 4061 02:42:53,680 --> 02:42:54,880 JUST ONE FIELD HERE. 4062 02:42:54,880 --> 02:42:58,240 WE COULDN'T DO OUR WORK WITHOUT 4063 02:42:58,240 --> 02:43:01,120 OUR COLLEAGUES IN CHEMISTRY, TO 4064 02:43:01,120 --> 02:43:03,000 VALIDATE CHEMICALS THAT WE'RE 4065 02:43:03,000 --> 02:43:04,160 GOING TO ANALYZE IN NAMs. 4066 02:43:04,160 --> 02:43:08,000 IT'S REALLY A LOT OF HARD WORK. 4067 02:43:08,000 --> 02:43:12,600 I GIVE ALL THE RESPECT TO MY 4068 02:43:12,600 --> 02:43:14,880 COLLEAGUES THERE THAT WORK ON 4069 02:43:14,880 --> 02:43:17,680 THESE MANY APPLICATIONS, THAT'S 4070 02:43:17,680 --> 02:43:19,040 AN UNDERSTATEMENT. 4071 02:43:19,040 --> 02:43:21,120 AND SO BUT ALSO THE POINT HERE 4072 02:43:21,120 --> 02:43:23,720 TOO IS THAT WE'RE KEEPING PUBLIC 4073 02:43:23,720 --> 02:43:27,360 HEALTH IN MIND AND OUR 4074 02:43:27,360 --> 02:43:28,680 REGULATION, REGULATORY LAW, AND 4075 02:43:28,680 --> 02:43:32,840 SO THAT COMES INTO PLAY WHEN 4076 02:43:32,840 --> 02:43:34,720 WE'RE CONSIDERING HOW TO APPLY 4077 02:43:34,720 --> 02:43:36,440 THESE PRODUCTS OR THESE NAMs 4078 02:43:36,440 --> 02:43:37,440 TO THE PRODUCTS. 4079 02:43:37,440 --> 02:43:40,720 AND I THINK WE ALL PROBABLY HAVE 4080 02:43:40,720 --> 02:43:42,880 HEARD OR KNOW ABOUT CIGARETTES 4081 02:43:42,880 --> 02:43:43,880 BUT MANY MAY NOT BE FAMILIAR 4082 02:43:43,880 --> 02:43:48,080 WITH SOME OF THE OTHER PRODUCTS. 4083 02:43:48,080 --> 02:43:49,120 THIS GIVES A PICTURE OF WHAT 4084 02:43:49,120 --> 02:43:54,720 SOME OTHER THINGS LOOK LIKE. 4085 02:43:54,720 --> 02:44:01,600 IT'S A HIGH DIVERSITY, WIDE 4086 02:44:01,600 --> 02:44:05,000 SPECTRUM, EVEN WITH E-CIGS. 4087 02:44:05,000 --> 02:44:08,040 THAT TAKES US TO A PICTURE OF 4088 02:44:08,040 --> 02:44:11,600 DEALING WITH A MYRIAD OF 4089 02:44:11,600 --> 02:44:14,320 CHEMICALS, SYNTHETICS, FOR 4090 02:44:14,320 --> 02:44:16,760 EXAMPLE, WITH E-CIGARETTES, A 4091 02:44:16,760 --> 02:44:18,880 RECENT REPORT BY JOHNS HOPKINS 4092 02:44:18,880 --> 02:44:21,640 UNIVERSITY SCHOOL OF PUBLIC 4093 02:44:21,640 --> 02:44:23,600 HEALTH THAT IDENTIFIED ALMOST 4094 02:44:23,600 --> 02:44:28,640 2,000 CHEMICALS IN AEROSOL OF 4095 02:44:28,640 --> 02:44:31,480 e-CIGS AND e-LIQUIDS, VERY 4096 02:44:31,480 --> 02:44:35,320 DAUNTING AND SETS THE STAGE FOR 4097 02:44:35,320 --> 02:44:38,600 USING NAMs GIVEN ALL THE 4098 02:44:38,600 --> 02:44:42,080 PRESENTATIONS WE'VE HEARD TODAY 4099 02:44:42,080 --> 02:44:43,960 AND YESTERDAY, EVEN PREVIOUS 4100 02:44:43,960 --> 02:44:47,040 PUBLIC FORUMS, WHERE THERE'S 4101 02:44:47,040 --> 02:44:52,480 REALLY CAPABILITY FOR 4102 02:44:52,480 --> 02:44:53,400 HIGH-THROUGHPUT ASSESSMENT 4103 02:44:53,400 --> 02:44:53,680 STRATEGIES. 4104 02:44:53,680 --> 02:44:56,320 AND SO WE ALSO WANTS TO BE 4105 02:44:56,320 --> 02:44:58,840 MAKING EVIDENCE BASED DECISIONS 4106 02:44:58,840 --> 02:45:04,840 AND I THINK NAMs CAN MEET THAT 4107 02:45:04,840 --> 02:45:06,160 CHALLENGE AND MOVE FORWARD WITH 4108 02:45:06,160 --> 02:45:08,680 USING THEM IN A PROGRAMMATIC AND 4109 02:45:08,680 --> 02:45:11,200 OPERATIONAL WAY TO INFORM OUR 4110 02:45:11,200 --> 02:45:13,160 TOBACCO REGULATORY SCIENCE. 4111 02:45:13,160 --> 02:45:15,000 THAT'S CRITICAL. 4112 02:45:15,000 --> 02:45:19,400 CRITICAL TO UNDERSTANDING IMPACT 4113 02:45:19,400 --> 02:45:20,640 ON VARIOUS ASPECTS OF TOBACCO 4114 02:45:20,640 --> 02:45:22,720 PRODUCTS ON PUBLIC HEALTH. 4115 02:45:22,720 --> 02:45:25,960 AND SO THIS IS JUST TO SAY WE'RE 4116 02:45:25,960 --> 02:45:29,120 VERY DEDICATED TO AN EVIDENCE 4117 02:45:29,120 --> 02:45:30,760 BASED ANALYSIS. 4118 02:45:30,760 --> 02:45:32,960 THE OTHER THING HERE LIKE I SAID 4119 02:45:32,960 --> 02:45:35,800 EARLIER I WANT YOU TO TAKE HOME 4120 02:45:35,800 --> 02:45:36,840 ABOUT PROGRAMMATIC APPROACH, AND 4121 02:45:36,840 --> 02:45:41,400 SO IF YOU WERE TO REDUCE ALL THE 4122 02:45:41,400 --> 02:45:42,600 ACTIVITIES THAT WE DO, NOT ALL 4123 02:45:42,600 --> 02:45:44,240 BUT THE ONES YOU COULD THINK OF 4124 02:45:44,240 --> 02:45:46,760 AT LEAST INTO FOUR PARTS, THIS 4125 02:45:46,760 --> 02:45:50,920 WOULD BE ONE WAY TO LOOK EIGHT. 4126 02:45:50,920 --> 02:45:52,760 APPLIED RESEARCH, REGULATORY 4127 02:45:52,760 --> 02:45:54,200 SCIENCE, APPLICATION REVIEW, AND 4128 02:45:54,200 --> 02:45:56,280 THEN WE'LL-WORLD PUBLIC HEALTH 4129 02:45:56,280 --> 02:45:58,760 IMPACT, WHICH IS WHAT WE'RE HERE 4130 02:45:58,760 --> 02:45:59,640 TODAY FOR. 4131 02:45:59,640 --> 02:46:01,040 AND SO NAMs IS AT THE 4132 02:46:01,040 --> 02:46:02,840 INTERSECTION OF ALL OF THESE. 4133 02:46:02,840 --> 02:46:06,000 SO IF YOU CAN IMAGINE WE CAN SEE 4134 02:46:06,000 --> 02:46:09,080 THE LOGIC IN DEVELOPING METHOD 4135 02:46:09,080 --> 02:46:12,800 FOR NAMs IN APPLIED RESEARCH, 4136 02:46:12,800 --> 02:46:14,120 COLLEAGUES AT NICEATM, ET 4137 02:46:14,120 --> 02:46:15,640 CETERA, AND THAT TO HELP INFORM 4138 02:46:15,640 --> 02:46:17,600 AND IMPROVE OUR REGULATORY 4139 02:46:17,600 --> 02:46:21,600 SCIENCE KNOWLEDGE BASE AND THEN 4140 02:46:21,600 --> 02:46:23,680 THAT IN TURN HELPS QUALITY OF 4141 02:46:23,680 --> 02:46:24,280 OUR REVIEWS. 4142 02:46:24,280 --> 02:46:27,680 SO THAT IN TURN WOULD TRANSLATE 4143 02:46:27,680 --> 02:46:29,120 INTO REAL WORLD HEALTH IMPACT. 4144 02:46:29,120 --> 02:46:31,640 BUT IT'S NOT TO SAY APPLIED 4145 02:46:31,640 --> 02:46:33,160 RESEARCH CAN'T MAKE A DIRECT 4146 02:46:33,160 --> 02:46:35,000 PUBLIC HEALTH IMPACT. 4147 02:46:35,000 --> 02:46:35,280 IT SURE CAN. 4148 02:46:35,280 --> 02:46:37,960 AND SO REALLY JUST KIND OF THINK 4149 02:46:37,960 --> 02:46:40,520 OF THIS AS NAMs REALLY IS AT 4150 02:46:40,520 --> 02:46:44,640 THE HUB OF ALL OF THESE AREAS. 4151 02:46:44,640 --> 02:46:46,720 I FIRST TRIED TO INSTRUCT THIS 4152 02:46:46,720 --> 02:46:48,920 SLIDE AND THOUGHT DRAWING ARROWS 4153 02:46:48,920 --> 02:46:52,120 BUT IT DOESN'T WORK THAT WAY. 4154 02:46:52,120 --> 02:46:57,600 THERE REALLY IS A MESH BETWEEN 4155 02:46:57,600 --> 02:46:57,800 THESE. 4156 02:46:57,800 --> 02:46:58,800 SO, AGAIN, APPLIED RESEARCH WE 4157 02:46:58,800 --> 02:47:02,400 TALK A LOT ABOUT THAT. 4158 02:47:02,400 --> 02:47:03,040 IT'S VERY MULTI-FACETED BECAUSE 4159 02:47:03,040 --> 02:47:06,640 TECHNOLOGIES, THERE ARE MANY 4160 02:47:06,640 --> 02:47:08,480 KIND OF TECHNOLOGIES BUT ONE OF 4161 02:47:08,480 --> 02:47:11,480 THE GOALS HERE TOO IS TO HELP 4162 02:47:11,480 --> 02:47:13,320 INFORM OUR POLICY DEVELOPMENT SO 4163 02:47:13,320 --> 02:47:15,880 WE CAN MAKE BETTER DECISIONS. 4164 02:47:15,880 --> 02:47:19,120 SO I WANT TO SHIFT GEARS NOW TO 4165 02:47:19,120 --> 02:47:22,760 THE RESEARCH AND WHERE WE'RE 4166 02:47:22,760 --> 02:47:24,160 ENGAGED AT CTP, EXAMPLES, AND I 4167 02:47:24,160 --> 02:47:26,800 WON'T BE ABLE TO SHOW EVERY 4168 02:47:26,800 --> 02:47:28,440 PROJECT, NOT ENOUGH TIME, BUT I 4169 02:47:28,440 --> 02:47:29,600 THOUGHT THIS IS VERY 4170 02:47:29,600 --> 02:47:30,960 INTERESTING. 4171 02:47:30,960 --> 02:47:32,600 IT'S A BROAD AGENCY ANNOUNCEMENT 4172 02:47:32,600 --> 02:47:36,960 WHICH WE FUNDED, AND WE HAVE A 4173 02:47:36,960 --> 02:47:40,600 TEAM OF TOXICOLOGISTS, WORKING 4174 02:47:40,600 --> 02:47:41,480 TOGETHER, WITH THE COLLABORATOR. 4175 02:47:41,480 --> 02:47:49,760 THIS IS AT THE UNIVERSITY OF 4176 02:47:49,760 --> 02:47:57,560 PITTSBURGH DEVELOPING A HUMAN 4177 02:47:57,560 --> 02:47:59,000 VAPING MEMETIC ANALYZER, ONGOING 4178 02:47:59,000 --> 02:48:01,160 FOR A WHILE. 4179 02:48:01,160 --> 02:48:01,720 THERE'S SOME PAPERS THAT 4180 02:48:01,720 --> 02:48:04,400 BASICALLY THE POINT HERE IS TO 4181 02:48:04,400 --> 02:48:07,840 HELP US -- ENABLING TECHNOLOGY 4182 02:48:07,840 --> 02:48:11,840 TO HELP US UNDERSTAND THE 4183 02:48:11,840 --> 02:48:14,360 PARTICLE SIZE IN AEROSOL, WHICH 4184 02:48:14,360 --> 02:48:16,600 RESEARCH HAS SHOWN THAT WITH 4185 02:48:16,600 --> 02:48:18,880 VITAMIN E AND MENTHOL CAN 4186 02:48:18,880 --> 02:48:21,160 INCREASE PARTICLE SIZE AND THAT 4187 02:48:21,160 --> 02:48:25,680 WOULD BE OBVIOUSLY NOT A GOOD 4188 02:48:25,680 --> 02:48:27,120 THING TO INCREASE THAT THIS IS 4189 02:48:27,120 --> 02:48:29,080 AN ILLUSTRATION WHAT IT LOOKS 4190 02:48:29,080 --> 02:48:29,560 LIKE. 4191 02:48:29,560 --> 02:48:32,560 IT'S A VAPING ROBOT. 4192 02:48:32,560 --> 02:48:35,640 AND SO, AGAIN, THIS IS A LOT OF 4193 02:48:35,640 --> 02:48:38,000 BIOMEDICAL ENGINEERING. 4194 02:48:38,000 --> 02:48:41,120 SOME LATEST RESEARCH HAS SHOWN, 4195 02:48:41,120 --> 02:48:44,080 HERE ARE SOME PAPERS, THAT WITH 4196 02:48:44,080 --> 02:48:48,880 ADDITION OF MENTHOL VERSUS 4197 02:48:48,880 --> 02:48:51,440 NON-MENTHOL, IT INCREASES 4198 02:48:51,440 --> 02:48:56,120 DISTRIBUTION SIZE, THE ANALYZER 4199 02:48:56,120 --> 02:48:59,320 CAN MEASURE FOUR DIFFERENT 4200 02:48:59,320 --> 02:49:00,520 MICRON-TO-MICRON SIZES OF 4201 02:49:00,520 --> 02:49:02,800 PARTICLES AND ANOTHER PRIOR 4202 02:49:02,800 --> 02:49:05,880 STUDY WHICH CTP PARTICIPATED IN 4203 02:49:05,880 --> 02:49:08,200 AUTHORSHIP WHICH IS WITH VITAMIN 4204 02:49:08,200 --> 02:49:11,400 E ADDITION, IT LED TO INCREASE 4205 02:49:11,400 --> 02:49:12,640 OF PARTICLES. 4206 02:49:12,640 --> 02:49:17,360 AND SO THAT WAS RELEVANT BECAUSE 4207 02:49:17,360 --> 02:49:20,520 OF THE ELECTRONIC CIGARETTE 4208 02:49:20,520 --> 02:49:23,800 VAPING ASSOCIATED LUNG INJURY 4209 02:49:23,800 --> 02:49:27,680 OUTBREAK THAT OCCURRED IN 2021, 4210 02:49:27,680 --> 02:49:30,920 AND SO -- ACTUALLY 2019. 4211 02:49:30,920 --> 02:49:32,760 ESSENTIALLY THESE SYSTEMS WE 4212 02:49:32,760 --> 02:49:35,960 THINK ARE GOING THE WAY OF 4213 02:49:35,960 --> 02:49:39,040 REALLY FINE TUNING AND HELPING 4214 02:49:39,040 --> 02:49:43,000 US UNDERSTAND THE IMPACT OF 4215 02:49:43,000 --> 02:49:44,760 THESE CONSTITUENTS OF THESE 4216 02:49:44,760 --> 02:49:46,160 COMPLEX MIXTURES, VERY 4217 02:49:46,160 --> 02:49:46,920 DIFFICULT. 4218 02:49:46,920 --> 02:49:49,560 I THINK IT WAS COMMENTED EARLIER 4219 02:49:49,560 --> 02:49:53,040 THEY VERY DIFFICULT TO ASSESS. 4220 02:49:53,040 --> 02:49:55,760 SO THIS IS A NEW 4221 02:49:55,760 --> 02:49:56,400 NEUROTECHNOLOGY, WE'RE CERTAINLY 4222 02:49:56,400 --> 02:49:59,720 ENGAGED HERE AND REALLY HAPPY 4223 02:49:59,720 --> 02:50:00,840 ABOUT THE PROGRESS. 4224 02:50:00,840 --> 02:50:10,040 SO WITH THAT I WANT TO TALK MORE 4225 02:50:10,040 --> 02:50:11,040 ABOUT COMPUTATIONAL MODEL. 4226 02:50:11,040 --> 02:50:12,000 WE DO USE ARTIFICIAL 4227 02:50:12,000 --> 02:50:15,200 INTELLIGENCE BUT IN THE CONTEXT 4228 02:50:15,200 --> 02:50:16,600 OF SUBSET OF IT, MACHINE 4229 02:50:16,600 --> 02:50:17,920 LEARNING, AND THE GOAL HERE 4230 02:50:17,920 --> 02:50:22,280 AGAIN IS TO MAKE BETTER 4231 02:50:22,280 --> 02:50:24,840 DECISIONS. 4232 02:50:24,840 --> 02:50:27,240 SO, BY INCORPORATING INTO OUR 4233 02:50:27,240 --> 02:50:32,080 PROGRAMMATIC AND EXTRA -- 4234 02:50:32,080 --> 02:50:34,320 STRATEGIC PLANS AND WE THINK WE 4235 02:50:34,320 --> 02:50:35,400 CAN IMPROVE ON THE INFORMATION 4236 02:50:35,400 --> 02:50:38,320 BASE TO MAKE BETTER DECISIONS. 4237 02:50:38,320 --> 02:50:39,080 THAT'S THE GOAL. 4238 02:50:39,080 --> 02:50:40,800 AND I THINK EVERYBODY HAS HEARD 4239 02:50:40,800 --> 02:50:42,360 ABOUT A.I. 4240 02:50:42,360 --> 02:50:45,320 THERE'S A LOT OF DIFFERENT KINDS 4241 02:50:45,320 --> 02:50:47,160 OF A.I. 4242 02:50:47,160 --> 02:50:51,400 AND SO THE APPROACHES THAT WE'RE 4243 02:50:51,400 --> 02:50:53,000 USING ARE INFORMATIC BASED. 4244 02:50:53,000 --> 02:50:54,480 WE'VE HEARD ABOUT OPERA, WHICH 4245 02:50:54,480 --> 02:50:56,240 LOOKS LIKE A VERY INTERESTING 4246 02:50:56,240 --> 02:50:56,600 SYSTEM. 4247 02:50:56,600 --> 02:50:59,040 I'LL FOLLOW UP WITH MY 4248 02:50:59,040 --> 02:51:01,600 COLLEAGUES AT NICEATM BECAUSE 4249 02:51:01,600 --> 02:51:03,120 IT'S A TRANSPARENT SYSTEM. 4250 02:51:03,120 --> 02:51:05,000 BUT THESE ALGORITHMS THAT DRIVE 4251 02:51:05,000 --> 02:51:06,920 THESE SYSTEMS ARE COMMON AND 4252 02:51:06,920 --> 02:51:08,520 HAVE BEEN USED MANY OTHER 4253 02:51:08,520 --> 02:51:11,040 INDUSTRIES FOR A LONG TIME. 4254 02:51:11,040 --> 02:51:15,080 AND SO I THINK IT IS A GREAT 4255 02:51:15,080 --> 02:51:17,160 THING TOXICOLOGY TAKES ADVANTAGE 4256 02:51:17,160 --> 02:51:21,400 TO HARNESS AND TO HELP LEVERAGE 4257 02:51:21,400 --> 02:51:23,600 EXISTING DATA, AND AVOID FURTHER 4258 02:51:23,600 --> 02:51:25,200 ANIMAL TESTING. 4259 02:51:25,200 --> 02:51:26,640 SO THAT'S SORT WHERE WE'RE 4260 02:51:26,640 --> 02:51:30,840 COMING FROM IN TERMS OF USING 4261 02:51:30,840 --> 02:51:33,360 COMPUTATIONAL TOXICOLOGY RIGHT 4262 02:51:33,360 --> 02:51:33,640 NOW. 4263 02:51:33,640 --> 02:51:37,040 WE'RE USING SOME COMMERCIAL 4264 02:51:37,040 --> 02:51:39,480 SYSTEMS, AND WITH THAT WE HAVE 4265 02:51:39,480 --> 02:51:41,920 DONE SOME RESEARCH. 4266 02:51:41,920 --> 02:51:46,120 THIS WAS LED BY DR. GOAL IN OUR 4267 02:51:46,120 --> 02:51:49,560 DIVISION, AND WAS PUBLISHED LAST 4268 02:51:49,560 --> 02:51:49,760 YEAR. 4269 02:51:49,760 --> 02:51:51,840 IT'S A SCREENING OF FLAVORS, 4270 02:51:51,840 --> 02:51:54,920 SINCE FLAVORS ARE COMMONLY FOUND 4271 02:51:54,920 --> 02:51:57,320 IN e-CIGARETTES, DEVELOPED A 4272 02:51:57,320 --> 02:52:02,240 LIBRARY OF OVER 3,000 CHEMICALLY 4273 02:52:02,240 --> 02:52:10,000 DEFINED FLAVORS, TO SCREEN FOR 4274 02:52:10,000 --> 02:52:10,680 RESPIRATORY TOXIFORES, USING 4275 02:52:10,680 --> 02:52:20,520 STRATEGY WHETHER COMPOUNDS HAVE 4276 02:52:20,520 --> 02:52:22,760 GHS, GLOBALLY HARMONIZED SYSTEM, 4277 02:52:22,760 --> 02:52:24,360 TO CHARACTERIZE THAT, AND SO THE 4278 02:52:24,360 --> 02:52:25,840 RESULTS, I DON'T HAVE THEM ALL 4279 02:52:25,840 --> 02:52:29,000 HERE BUT I THOUGHT TO SHOW YOU 4280 02:52:29,000 --> 02:52:32,520 SOME OF THEM, YOU KNOW, A LARGE 4281 02:52:32,520 --> 02:52:34,040 PERCENTAGE OF THESE HAVE, IF WE 4282 02:52:34,040 --> 02:52:39,000 APPLY THAT CRITERIA TO THIS, AND 4283 02:52:39,000 --> 02:52:41,080 ANOTHER TECHNIQUE THAT WAS USED 4284 02:52:41,080 --> 02:52:45,080 MOLECULAR FILTERING, SO THIS IS 4285 02:52:45,080 --> 02:52:47,000 VERY HIGH-THROUGHPUT, AND 4286 02:52:47,000 --> 02:52:48,840 ESSENTIALLY YOU CAN INSERT A 4287 02:52:48,840 --> 02:52:50,360 REACTIVE GROUP, LET'S SAY YOU'RE 4288 02:52:50,360 --> 02:52:52,880 INTERESTED IN, THE IDEA HERE IS 4289 02:52:52,880 --> 02:52:55,960 WE'RE NOT DOING THIS REALTIME 4290 02:52:55,960 --> 02:52:57,360 FOR OUR APPLICATION REVIEW OF 4291 02:52:57,360 --> 02:52:57,760 COURSE. 4292 02:52:57,760 --> 02:53:03,000 BUT THE IDEA HERE IS TO PERHAPS 4293 02:53:03,000 --> 02:53:03,680 DEMONSTRATE TO OUR STAKEHOLDERS, 4294 02:53:03,680 --> 02:53:05,240 MAYBE THIS IS SOMETHING THAT 4295 02:53:05,240 --> 02:53:08,880 COULD BE DONE TO HELP MITIGATE 4296 02:53:08,880 --> 02:53:11,200 THE RISKS, HELP MITIGATE TO 4297 02:53:11,200 --> 02:53:12,280 REDUCE THIS, SINCE THIS GOES 4298 02:53:12,280 --> 02:53:17,240 BACK TO THE MISSION STATEMENT OF 4299 02:53:17,240 --> 02:53:19,000 REDUCING HARM. 4300 02:53:19,000 --> 02:53:21,920 SO SCREENING, EARLY DETECTION 4301 02:53:21,920 --> 02:53:23,000 SYSTEMS, WHICH COMPUTATIONAL 4302 02:53:23,000 --> 02:53:24,200 SYSTEMS ARE REALLY ALL ABOUT 4303 02:53:24,200 --> 02:53:28,480 COULD BE HELPFUL. 4304 02:53:28,480 --> 02:53:29,920 HERE'S ANOTHER SITUATION, WELL 4305 02:53:29,920 --> 02:53:33,600 KNOWN FOR THE OCCUPATIONAL 4306 02:53:33,600 --> 02:53:41,480 EXPOSURE ISSUE YEARS AGO, WITH 4307 02:53:41,480 --> 02:53:45,080 POPCORN LUNG DISEASE, DAACETYL. 4308 02:53:45,080 --> 02:53:47,960 THERE'S ANALOGS CLOSELY RELATED, 4309 02:53:47,960 --> 02:53:50,480 THIS WOULD SAY, WHEN ASKED THE 4310 02:53:50,480 --> 02:53:53,680 QUESTION WHY WOULD I WANT TO ADD 4311 02:53:53,680 --> 02:53:58,120 THIS COMPOUND TO THIS e-LIQUID 4312 02:53:58,120 --> 02:53:59,280 IN ABSENCE OF EXPERIMENTAL 4313 02:53:59,280 --> 02:54:01,640 TESTING, THIS IS SORT OF WHAT 4314 02:54:01,640 --> 02:54:03,520 THE PHARMACEUTICAL INDUSTRY DOES 4315 02:54:03,520 --> 02:54:06,680 IS IN THE EARLY STAGES OF 4316 02:54:06,680 --> 02:54:12,720 DISCOVERY, TO TRY TO REDUCE ARM, 4317 02:54:12,720 --> 02:54:15,560 MITIGATE LIABILITY. 4318 02:54:15,560 --> 02:54:17,200 THEY ARE CHEMISTRY DRIVEN, DATA 4319 02:54:17,200 --> 02:54:18,520 DRIVEN, WE'RE INTERESTED IN 4320 02:54:18,520 --> 02:54:19,640 EXPLORING THAT. 4321 02:54:19,640 --> 02:54:25,240 AND THIS IS ANOTHER PROCEDURE 4322 02:54:25,240 --> 02:54:26,880 USING COMMON SUBSTRUCTURES TO 4323 02:54:26,880 --> 02:54:30,800 IDENTIFY, YOU CAN APPLY A LOT OF 4324 02:54:30,800 --> 02:54:32,240 CRITERIA THAT WOULD BE UP TO -- 4325 02:54:32,240 --> 02:54:35,120 IF IT'S AN INDUSTRY OR WHOEVER 4326 02:54:35,120 --> 02:54:39,760 IS DEVELOPING A PRODUCT, TO MAKE 4327 02:54:39,760 --> 02:54:49,080 THOSE DECISIONS BEFORE THEY 4328 02:54:49,080 --> 02:54:49,600 DEVELOP THINGS. 4329 02:54:49,600 --> 02:54:51,280 THERE'S A LOT OF TECHNIQUES 4330 02:54:51,280 --> 02:54:52,440 BEGINNING WITH CHEMISTRY. 4331 02:54:52,440 --> 02:54:57,200 GETTING BACK TO WHAT I WANTED TO 4332 02:54:57,200 --> 02:55:00,920 EMPHASIZE TODAY, ABOUT 4333 02:55:00,920 --> 02:55:01,720 PROGRAMMATIC APPROACH, WE 4334 02:55:01,720 --> 02:55:10,680 ESSENTIALLY ESTABLISHED A TEAM, 4335 02:55:10,680 --> 02:55:16,360 NON-CLINICAL COMPUTATIONAL 4336 02:55:16,360 --> 02:55:18,520 TOXICOLOGY TEAM, NCTP, A GREAT 4337 02:55:18,520 --> 02:55:21,040 BRIGHT TEAM OF SCIENTISTS IN OUR 4338 02:55:21,040 --> 02:55:26,200 DIVISION THAT'S DEDICATED TO 4339 02:55:26,200 --> 02:55:27,840 SERVICING AND SUPPORTING 4340 02:55:27,840 --> 02:55:31,560 BASICALLY ACTIVITIES IN 4341 02:55:31,560 --> 02:55:40,120 PROGRAMMATIC AREAS FROM RESEARCH 4342 02:55:40,120 --> 02:55:40,960 TRAINING & EDUCATION, 4343 02:55:40,960 --> 02:55:41,640 COLLABORATION, AN INTERNAL GROUP 4344 02:55:41,640 --> 02:55:43,080 AND REVIEWS SUPPORT, A PRIMARY 4345 02:55:43,080 --> 02:55:44,600 FOCUS RIGHT NOW. 4346 02:55:44,600 --> 02:55:51,800 IF WE HAVE A REVIEWER THEY GET 4347 02:55:51,800 --> 02:55:52,480 COMPUTATIONAL TOXICOLOGY DATA, 4348 02:55:52,480 --> 02:55:53,920 THIS TEAM IS THERE TO SUPPORT 4349 02:55:53,920 --> 02:55:55,680 THEM TO HELP ANSWER THEIR 4350 02:55:55,680 --> 02:55:55,960 QUESTIONS. 4351 02:55:55,960 --> 02:55:58,200 OH, OKAY, WHAT DO DO YOU IF YOU 4352 02:55:58,200 --> 02:56:01,840 GET A PREDICTION, HOW DO I 4353 02:56:01,840 --> 02:56:03,680 APPRAISE THAT INFORMATION? 4354 02:56:03,680 --> 02:56:04,520 THINGS LIKE THAT. 4355 02:56:04,520 --> 02:56:06,880 STAYING ON TOP OF THE 4356 02:56:06,880 --> 02:56:08,280 TECHNOLOGY, YOU KNOW, DOING 4357 02:56:08,280 --> 02:56:11,440 TRAINING FOR THEMSELVES TO KEEP 4358 02:56:11,440 --> 02:56:13,760 UP WITH IT. 4359 02:56:13,760 --> 02:56:17,480 AND SO BASICALLY, YOU KNOW, IT'S 4360 02:56:17,480 --> 02:56:18,760 A PROGRAMMATIC APPROACH TO 4361 02:56:18,760 --> 02:56:22,280 SUPPORT OURSELVES SO THAT WE CAN 4362 02:56:22,280 --> 02:56:29,520 DO A BETTER JOB AND EVALUATE 4363 02:56:29,520 --> 02:56:30,640 THESE PRODUCTS MUCH BETTER. 4364 02:56:30,640 --> 02:56:32,080 A BIG PLUG FOR THEM, PRIVILEGED 4365 02:56:32,080 --> 02:56:33,440 AND DELIGHTED TO BE ABLE TO WORK 4366 02:56:33,440 --> 02:56:37,160 WITH THEM. 4367 02:56:37,160 --> 02:56:38,120 SO HAPPY ABOUT THAT. 4368 02:56:38,120 --> 02:56:40,680 A LOT OF THINGS LISTED ARE 4369 02:56:40,680 --> 02:56:42,880 ALREADY WELL KNOWN BY THIS 4370 02:56:42,880 --> 02:56:43,120 AUDIENCE. 4371 02:56:43,120 --> 02:56:46,120 BUT I DID WANT TO MAKE THE POINT 4372 02:56:46,120 --> 02:56:48,200 THAT AT CTP WHAT WE'RE DOING 4373 02:56:48,200 --> 02:56:51,360 WITH NAMs DOES REFLECT THE 4374 02:56:51,360 --> 02:56:54,240 GOALS OF THE PREDICTIVE TOX ROAD 4375 02:56:54,240 --> 02:56:55,680 MAP RELEASED IN 2017. 4376 02:56:55,680 --> 02:56:58,080 SO EVERYBODY KNOWS ABOUT 4377 02:56:58,080 --> 02:56:59,400 EFFICIENCY, THINGS LIKE THAT. 4378 02:56:59,400 --> 02:57:00,800 BUT WE'RE ALSO THINKING ABOUT 4379 02:57:00,800 --> 02:57:04,200 THIS AS A STRATEGY TO SUPPORT 4380 02:57:04,200 --> 02:57:04,800 PRIORITIZATION FOR FOLLOW-UP, 4381 02:57:04,800 --> 02:57:07,040 THANKED DOESN'T NECESSARILY MEAN 4382 02:57:07,040 --> 02:57:07,400 TESTING. 4383 02:57:07,400 --> 02:57:09,680 IT MIGHT MEAN FOLLOW-UP MORE 4384 02:57:09,680 --> 02:57:13,960 LITERATURE, THERE ARE OTHER 4385 02:57:13,960 --> 02:57:15,640 DIFFERENT WAYS, READ ACROSS, FOR 4386 02:57:15,640 --> 02:57:15,920 EXAMPLE. 4387 02:57:15,920 --> 02:57:19,120 PART OF THE -- SPEAKING OF THAT, 4388 02:57:19,120 --> 02:57:21,280 WE'RE ALSO DOING OUTREACH WITH 4389 02:57:21,280 --> 02:57:23,800 OUR OTHER CENTERS LIKE CFSAN, 4390 02:57:23,800 --> 02:57:26,640 WE'VE STARTED TO WORK WITH THEM. 4391 02:57:26,640 --> 02:57:28,080 THEY HAVE A COMPUTATIONAL 4392 02:57:28,080 --> 02:57:29,920 TOXICOLOGY GROUP AND SO TO HELP 4393 02:57:29,920 --> 02:57:31,040 HARMONIZE AND LEARN FROM THEM, 4394 02:57:31,040 --> 02:57:35,960 THEY HAVE BEEN DOING IT FOR A 4395 02:57:35,960 --> 02:57:36,280 LONG TIME. 4396 02:57:36,280 --> 02:57:39,160 AND SO AGAIN GETTING BACK TO THE 4397 02:57:39,160 --> 02:57:41,200 OVERALL STRATEGY FOR EVERYBODY'S 4398 02:57:41,200 --> 02:57:42,440 LEVERAGE EXISTING KNOWLEDGE SO 4399 02:57:42,440 --> 02:57:45,800 WE CAN REDUCE ANIMAL TESTING AND 4400 02:57:45,800 --> 02:57:47,080 MAXIMIZE RESOURCES AND USE THE 4401 02:57:47,080 --> 02:57:51,160 BEST TECHNOLOGY THAT WE CAN. 4402 02:57:51,160 --> 02:57:52,280 THAT SOUNDS GREAT BUT WE ALSO 4403 02:57:52,280 --> 02:57:57,600 HAVE TO KEEP THINGS IN MIND. 4404 02:57:57,600 --> 02:57:58,280 AND THAT'S CONSIDERATIONS, NOT 4405 02:57:58,280 --> 02:58:00,040 PERFECT, ONE OF THE BIG THINGS 4406 02:58:00,040 --> 02:58:04,600 WE'RE LOOKING AT RIGHT NOW ARE 4407 02:58:04,600 --> 02:58:05,400 HUMAN EXPERT REVIEW PREDICTIONS, 4408 02:58:05,400 --> 02:58:08,000 AND SO WE DON'T JUST LOOK AT 4409 02:58:08,000 --> 02:58:09,560 PREDICTION AND SAY COMPUTER SAID 4410 02:58:09,560 --> 02:58:15,640 THAT, SO WE'LL MOVE FORWARD. 4411 02:58:15,640 --> 02:58:18,000 WE WANT EXPLAINABILITY, 4412 02:58:18,000 --> 02:58:19,080 TRANSPARENCY, THE THINKING IS, 4413 02:58:19,080 --> 02:58:25,520 YOU KNOW, ONE SHOULD CONSIDER S 4414 02:58:25,520 --> 02:58:28,840 A MODEL FIT FOR THIS TECHNICAL 4415 02:58:28,840 --> 02:58:30,320 QUESTION, DIFFICULT TO 4416 02:58:30,320 --> 02:58:30,920 GENERALIZE MODEL OVER 4417 02:58:30,920 --> 02:58:31,280 EVERYTHING. 4418 02:58:31,280 --> 02:58:32,080 THIS IS SCIENCE. 4419 02:58:32,080 --> 02:58:34,360 SO THAT'S JUST THE WAY IT GOES. 4420 02:58:34,360 --> 02:58:38,520 WE HAVE TO MAKE SURE THAT THE 4421 02:58:38,520 --> 02:58:40,600 MODEL AND PREDICTION DATA IS 4422 02:58:40,600 --> 02:58:44,320 REALLY APPROPRIATE FOR THE DATA 4423 02:58:44,320 --> 02:58:45,840 CIRCUMSTANCE. 4424 02:58:45,840 --> 02:58:47,240 SO, YEAH, WE WANT EFFICIENCY BUT 4425 02:58:47,240 --> 02:58:50,680 NOT AT THE EXPENSE OF LESS 4426 02:58:50,680 --> 02:58:51,120 SCIENTIFIC RIGOR. 4427 02:58:51,120 --> 02:58:55,280 WE WANT RELIABILITY AND MAINTAIN 4428 02:58:55,280 --> 02:58:57,680 THE QUALITY AND INTEGRITY TO 4429 02:58:57,680 --> 02:58:59,200 FIELDING THE SCIENTIFIC QUESTION 4430 02:58:59,200 --> 02:58:59,880 AT HAND. 4431 02:58:59,880 --> 02:59:04,560 HERE IS THIS -- THIS IS A 4432 02:59:04,560 --> 02:59:05,560 THINKING ABOUT, AGAIN, GOING 4433 02:59:05,560 --> 02:59:07,400 BACK TO, FOR EXAMPLE, 4434 02:59:07,400 --> 02:59:10,160 QUANTITATIVE STRUCTURE ACTIVITY 4435 02:59:10,160 --> 02:59:12,440 RELATIONSHIP MODEL, QSAR, USING 4436 02:59:12,440 --> 02:59:16,200 THEM TO IDENTIFY DNA DAMAGE AND 4437 02:59:16,200 --> 02:59:19,360 THEN APPLYING HUMAN EXPERT 4438 02:59:19,360 --> 02:59:21,440 KNOWLEDGE TO THAT PREDICTIVE 4439 02:59:21,440 --> 02:59:23,840 DATA, AND THEN TAKE A WEIGHT OF 4440 02:59:23,840 --> 02:59:25,680 EVIDENCE APPROACH AND WHAT WE'RE 4441 02:59:25,680 --> 02:59:29,640 LOOKING AT RIGHT, THERE ARE 4442 02:59:29,640 --> 02:59:30,200 OTHER ENDPOINTS OBVIOUSLY, 4443 02:59:30,200 --> 02:59:31,120 RESPIRATORY TOXICITY. 4444 02:59:31,120 --> 02:59:35,640 RIGHT NOW THERE'S QUITE A BIT OF 4445 02:59:35,640 --> 02:59:38,040 AVAILABILITY, IF YOU WILL, FOR 4446 02:59:38,040 --> 02:59:41,920 PREDICTIVE MODELS FOR THESE 4447 02:59:41,920 --> 02:59:44,480 ENDPOINTS BUT IT'S DIFFICULT TO 4448 02:59:44,480 --> 02:59:47,040 BUILD FRAMEWORK BECAUSE OF THE 4449 02:59:47,040 --> 02:59:49,360 DATA ISSUE, EVERY APPLICATION IS 4450 02:59:49,360 --> 02:59:49,840 DIFFERENT. 4451 02:59:49,840 --> 02:59:53,640 SO DATA, THERE MIGHT BE 4452 02:59:53,640 --> 02:59:54,600 INFORMATION ON XYZ TYPE OF 4453 02:59:54,600 --> 02:59:57,440 DAMAGE AND MAYBE NOT THE OTHER 4454 02:59:57,440 --> 02:59:57,760 KIND. 4455 02:59:57,760 --> 03:00:01,520 AND SO THERE REALLY IS A 4456 03:00:01,520 --> 03:00:02,360 CASE-BY-CASE BASIS. 4457 03:00:02,360 --> 03:00:05,240 BUT LIKE I SAID WE'RE REACHING 4458 03:00:05,240 --> 03:00:07,080 OUT WITH OUR COLLEAGUES AT OTHER 4459 03:00:07,080 --> 03:00:09,960 CENTERS TO LEARN FROM THEM AS 4460 03:00:09,960 --> 03:00:13,120 WELL AND TO -- WE'RE IN 4461 03:00:13,120 --> 03:00:13,960 DIFFERENT SITUATION, INHALATION 4462 03:00:13,960 --> 03:00:17,160 EXPOSURES, BUT ALTHOUGH WE HAVE 4463 03:00:17,160 --> 03:00:19,000 SMOKELESS EXPOSURES TOO WITH 4464 03:00:19,000 --> 03:00:20,640 OTHER PRODUCTS, SO THE OTHER 4465 03:00:20,640 --> 03:00:23,600 TAKEHOME HERE IS HOW WE'RE USING 4466 03:00:23,600 --> 03:00:26,120 THIS FOR CHEMICAL HAZARD I.D., 4467 03:00:26,120 --> 03:00:29,960 SO WITH THE QSARs, YOU'RE 4468 03:00:29,960 --> 03:00:32,600 FAMILIAR WITH THE RAISE THE RED 4469 03:00:32,600 --> 03:00:35,880 FLAG, THE WHOLE GOAL HERE IS TO 4470 03:00:35,880 --> 03:00:38,840 SEE IF THERE'S A CONCERN, HOW 4471 03:00:38,840 --> 03:00:40,680 CAN WE SET PRIORITIES, IS IT 4472 03:00:40,680 --> 03:00:42,880 NECESSARY TO FOLLOW UP, AND THAT 4473 03:00:42,880 --> 03:00:44,320 IS GOING TO ENHANCE OUR DECISION 4474 03:00:44,320 --> 03:00:46,600 MAKING AT THE LEVEL OF 4475 03:00:46,600 --> 03:00:47,560 REGULATORY REVIEW. 4476 03:00:47,560 --> 03:00:50,400 I KNOW I'M RUNNING A LITTLE BIT 4477 03:00:50,400 --> 03:00:53,160 SHORT OR LONG ON TIME. 4478 03:00:53,160 --> 03:00:56,640 SO I'M ALMOST DONE. 4479 03:00:56,640 --> 03:00:58,400 ESSENTIALLY, THIS HAS BEEN SAID 4480 03:00:58,400 --> 03:01:05,200 MANY TIMES AT THE ICCVAM AND FOR 4481 03:01:05,200 --> 03:01:08,880 GOOD REASON, CONTEXT OF USE IN 4482 03:01:08,880 --> 03:01:11,760 EVIDENCE-BASED WAY, AND THIS IS 4483 03:01:11,760 --> 03:01:12,000 TRUE. 4484 03:01:12,000 --> 03:01:14,520 THE WAY WE'RE LOOKING AT IT AND 4485 03:01:14,520 --> 03:01:18,320 MOVING FORWARD, OUR CALL TO 4486 03:01:18,320 --> 03:01:20,360 ACTION IS CONTINUALLY BETTERING 4487 03:01:20,360 --> 03:01:24,120 THE SCIENCE TO HELP SUPPORT OUR 4488 03:01:24,120 --> 03:01:26,840 REGULATORY TOX REVIEW EVALUATION 4489 03:01:26,840 --> 03:01:27,280 SITUATIONS. 4490 03:01:27,280 --> 03:01:30,440 THERE'S ISSUES THAT WE RUN INTO. 4491 03:01:30,440 --> 03:01:34,200 MAYBE DATA, THERE'S NO 4492 03:01:34,200 --> 03:01:35,920 PREDICTION NARRATIVE IF THE 4493 03:01:35,920 --> 03:01:39,080 APPLICANT SAYS IT'S POSITIVE, 4494 03:01:39,080 --> 03:01:43,480 NEGATIVE, FROM CLASSIFIER MODEL 4495 03:01:43,480 --> 03:01:43,920 MODEL 4496 03:01:43,920 --> 03:01:45,000 THAT MAY NOT GIVE ENOUGH 4497 03:01:45,000 --> 03:01:45,320 INFORMATION. 4498 03:01:45,320 --> 03:01:48,720 IS THE MODEL FIT FOR THAT 4499 03:01:48,720 --> 03:01:49,320 PURPOSE? 4500 03:01:49,320 --> 03:01:52,880 THIS IS WHERE LIKE WE'RE MOVING 4501 03:01:52,880 --> 03:01:54,600 THE DIRECTION AS WELL AS WORKING 4502 03:01:54,600 --> 03:01:55,760 ON WEIGHT OF EVIDENCE. 4503 03:01:55,760 --> 03:02:00,760 WE NEED TO BE CONSERVATIVE, TO 4504 03:02:00,760 --> 03:02:03,040 PROTECT POPULATION, AS I 4505 03:02:03,040 --> 03:02:05,360 MENTIONED BEFORE, AND UNDER THE 4506 03:02:05,360 --> 03:02:10,080 PMTA AND OTHER REGULATORY 4507 03:02:10,080 --> 03:02:10,480 PATHWAYS. 4508 03:02:10,480 --> 03:02:12,920 I THINK I'M BASICALLY DONE BUT I 4509 03:02:12,920 --> 03:02:15,680 WANT TO THANK -- THESE ARE THE 4510 03:02:15,680 --> 03:02:18,320 MEMBERS OF THE NCPT TEAM THAT'S 4511 03:02:18,320 --> 03:02:18,520 NEW. 4512 03:02:18,520 --> 03:02:23,920 IT'S A PLEASURE TO WORK WITH 4513 03:02:23,920 --> 03:02:25,200 THEM IN MY OFFICE. 4514 03:02:25,200 --> 03:02:26,840 SO THANK YOU FOR YOUR TIME. 4515 03:02:26,840 --> 03:02:28,720 I'M SURE YOU MIGHT HAVE A FEW 4516 03:02:28,720 --> 03:02:31,000 QUESTIONS AND I APPRECIATE IT. 4517 03:02:31,000 --> 03:02:33,200 [APPLAUSE] 4518 03:02:33,200 --> 03:02:35,040 4519 03:02:35,040 --> 03:02:36,840 >> THANK YOU, LUIS, EXCELLENT 4520 03:02:36,840 --> 03:02:37,200 PRESENTATION. 4521 03:02:37,200 --> 03:02:40,960 I KNOW THERE ARE A NUMBER OF 4522 03:02:40,960 --> 03:02:41,520 OPPORTUNITIES FOR FOLLOW-UP 4523 03:02:41,520 --> 03:02:42,920 BETWEEN OUR GROUPS. 4524 03:02:42,920 --> 03:02:44,600 YOU MENTIONED LOOKING AT OPERA, 4525 03:02:44,600 --> 03:02:47,680 ALSO SOME OUTCOMES OF THE 4526 03:02:47,680 --> 03:02:49,520 CLUSTERING AND CLASSIFICATION 4527 03:02:49,520 --> 03:02:52,320 WORKSHOP THAT DTT RAN IN THE 4528 03:02:52,320 --> 03:02:53,560 FALL ARE PARTICULARLY RELEVANT 4529 03:02:53,560 --> 03:02:57,560 TO SOME OF THE APPLICATIONS THAT 4530 03:02:57,560 --> 03:02:58,480 YOU DISCUSSED HERE, THINKING 4531 03:02:58,480 --> 03:03:00,240 ABOUT EXTENSION, YOU KNOW, NOT 4532 03:03:00,240 --> 03:03:03,400 SOLE RELIANCE ON GENERAL 4533 03:03:03,400 --> 03:03:04,600 SIMILARITY TECHNIQUES BUT 4534 03:03:04,600 --> 03:03:05,200 ENDPOINT-SPECIFIC SIMILARITY 4535 03:03:05,200 --> 03:03:06,240 TECHNIQUES AS WELL SO REALLY 4536 03:03:06,240 --> 03:03:07,440 LOOK FORWARD TO FOLLOWING UP ON 4537 03:03:07,440 --> 03:03:08,520 THAT AS WELL. 4538 03:03:08,520 --> 03:03:13,040 I'M SURE I CAN COUNT ON KAMEL 4539 03:03:13,040 --> 03:03:13,760 MANSOURI TO FOLLOW UP. 4540 03:03:13,760 --> 03:03:14,560 >>GREAT. 4541 03:03:14,560 --> 03:03:16,720 THANK YOU, NICOLE. 4542 03:03:16,720 --> 03:03:18,840 ANY OTHER QUESTIONS? 4543 03:03:18,840 --> 03:03:19,840 IS THERE ONE ONLINE? 4544 03:03:19,840 --> 03:03:23,520 >> YEAH, A QUESTION FROM JOE 4545 03:03:23,520 --> 03:03:32,360 FROM PCRM FOR YOUR LUIS, HOW CL 4546 03:03:32,360 --> 03:03:34,360 ARE STUDIES FOR ELECTRONIC 4547 03:03:34,360 --> 03:03:36,000 NICOTINE DELIVERY SYSTEMS GIVEN 4548 03:03:36,000 --> 03:03:38,840 THAT THEY HAVE STATED STATED 4549 03:03:38,840 --> 03:03:42,880 SUCH STUDIES ALONE -- I'M SORRY. 4550 03:03:42,880 --> 03:03:44,760 SUCH STUDIES ALONE WILL NOT 4551 03:03:44,760 --> 03:03:46,200 MEET, QUOTE, APPROPRIATE FOR 4552 03:03:46,200 --> 03:03:48,360 PROTECTION OF PUBLIC HEALTH 4553 03:03:48,360 --> 03:03:49,000 STANDARD, SPECIFICALLY HOW IS 4554 03:03:49,000 --> 03:03:55,480 ONE OF THE FIRST APPROVED 4555 03:03:55,480 --> 03:03:57,240 PMTAs ABLE TO SEEK APPROVAL 4556 03:03:57,240 --> 03:04:02,360 WHILE ANOTHER INCLUDED RAT 4557 03:04:02,360 --> 03:04:02,800 INHALATION STUDIES. 4558 03:04:02,800 --> 03:04:04,840 >> YEAH, THERE'S A LOT THERE IN 4559 03:04:04,840 --> 03:04:07,760 THAT QUESTION. 4560 03:04:07,760 --> 03:04:11,000 LET ME TRY TACKLE. 4561 03:04:11,000 --> 03:04:12,920 I CAN'T ANSWER THE QUESTION 4562 03:04:12,920 --> 03:04:18,680 ABOUT CARISA, MORE OF A QUESTION 4563 03:04:18,680 --> 03:04:22,520 FOR OUR CENTER BUT PMT FINAL 4564 03:04:22,520 --> 03:04:27,560 RULE WHICH CAME IN EFFECT 4565 03:04:27,560 --> 03:04:30,160 NOVEMBER BASICALLY SAYS THAT NOT 4566 03:04:30,160 --> 03:04:30,720 REQUIRED FOR APPLICATION 4567 03:04:30,720 --> 03:04:36,400 ACCEPTANCE OR FILING IT 4568 03:04:36,400 --> 03:04:38,400 RECOMMENDS TOXOLOGICAL STUDIES 4569 03:04:38,400 --> 03:04:45,160 ESPECIALLY THOSE ON CHRONIC 4570 03:04:45,160 --> 03:04:50,800 EFFECTS, AND SO IT'S IN -- 4571 03:04:50,800 --> 03:04:53,760 >>OH DEAR. 4572 03:04:53,760 --> 03:04:56,880 WE SEEM TO HAVE LOST DR. 4573 03:04:56,880 --> 03:04:57,400 VALERIO. 4574 03:04:57,400 --> 03:04:59,680 WE'LL GIVE IT A COUPLE MORE 4575 03:04:59,680 --> 03:05:00,040 SECONDS. 4576 03:05:00,040 --> 03:05:02,200 IF WE DON'T GET HIM BACK WE'LL 4577 03:05:02,200 --> 03:05:07,040 HAVE TO FOLLOW UP ONLINE. 4578 03:05:07,040 --> 03:05:11,600 4579 03:05:11,600 --> 03:05:12,520 YEAH, UNFORTUNATELY WE'LL HAVE 4580 03:05:12,520 --> 03:05:16,360 TO MOVE ON BECAUSE DR. VALERIO 4581 03:05:16,360 --> 03:05:18,520 HAS LOST CONNECTION, WE'LL BE 4582 03:05:18,520 --> 03:05:19,400 SURE TO PROVIDE THAT QUESTION 4583 03:05:19,400 --> 03:05:20,480 AND ANY OTHER QUESTIONS THAT 4584 03:05:20,480 --> 03:05:23,800 COME UP FOR HIM VIA E-MAIL AND 4585 03:05:23,800 --> 03:05:26,720 ENCOURAGE DIRECT FOLLOW-UP WITH 4586 03:05:26,720 --> 03:05:28,920 THE SUBMITTER. 4587 03:05:28,920 --> 03:05:32,000 SO, NEXT PRESENTATION IS FROM 4588 03:05:32,000 --> 03:05:42,480 DEPARTMENT OF DEFENSE, TYLER 4589 03:05:42,760 --> 03:05:44,480 GORALSKI ABOUT 4590 03:05:44,480 --> 03:05:45,080 SOLDIER-ON-A-CHIP. 4591 03:05:45,080 --> 03:05:47,000 CAN YOU SHARE YOUR SLIDES 4592 03:05:47,000 --> 03:05:48,840 PLEASE? 4593 03:05:48,840 --> 03:05:53,440 4594 03:05:53,440 --> 03:05:55,320 LOOKS PERFECT. 4595 03:05:55,320 --> 03:05:55,600 THANK YOU. 4596 03:05:55,600 --> 03:05:56,640 >> OKAY. 4597 03:05:56,640 --> 03:05:57,480 THANK YOU, NICOLE. 4598 03:05:57,480 --> 03:06:03,160 THANK YOU ALL FOR HAVING ME. 4599 03:06:03,160 --> 03:06:07,320 I'M TYLER GORALSKI, RESEARCH 4600 03:06:07,320 --> 03:06:07,960 BIOLOGIST WITH DEVCOM BIOLOGICAL 4601 03:06:07,960 --> 03:06:11,840 CENTER WHERE I MANAGE OUR MPS OR 4602 03:06:11,840 --> 03:06:15,120 ORGAN ON A CHIP STUDIES. 4603 03:06:15,120 --> 03:06:19,480 TODAY I'M GOING GIVE AN OVERVIEW 4604 03:06:19,480 --> 03:06:22,440 OF THE CAPABILITIES AND 4605 03:06:22,440 --> 03:06:23,320 SPECIFICALLY DESCRIBE OUR 4606 03:06:23,320 --> 03:06:24,520 EFFORTS TO INTERROGATE EFFECTS 4607 03:06:24,520 --> 03:06:28,400 OF CHEMICAL AND BIOLOGICAL 4608 03:06:28,400 --> 03:06:29,680 THREAT AGENTS USING A 4609 03:06:29,680 --> 03:06:39,800 MULTI-ORGAN ON A CHIP SYSTEM. 4610 03:06:39,800 --> 03:06:43,040 TO PROVIDE CONTEXT WHAT MY GROUP 4611 03:06:43,040 --> 03:06:46,280 DOES WE'RE FOCUSED ON PREDICTIVE 4612 03:06:46,280 --> 03:06:48,720 TOXICOLOGIES, WITH THAT WE 4613 03:06:48,720 --> 03:06:50,520 DEVELOP, ACQUIRE, IMPLEMENT IN 4614 03:06:50,520 --> 03:06:52,280 VITRO MODELS AND SYSTEMS THAT WE 4615 03:06:52,280 --> 03:06:54,600 CAN USE TO PERFORM TOXICOLOGICAL 4616 03:06:54,600 --> 03:06:57,440 ASSESSMENTS, AND WE USE DATA FOR 4617 03:06:57,440 --> 03:07:00,080 IT TO GUIDE DOWNSTREAM IN VIVO 4618 03:07:00,080 --> 03:07:01,160 ASSESSMENTS WITH HOPES OF 4619 03:07:01,160 --> 03:07:03,440 REDUCING NUMBER OF ANIMALS WE'RE 4620 03:07:03,440 --> 03:07:06,840 USING FOR THOSE STUDIES. 4621 03:07:06,840 --> 03:07:10,040 HERE I HAVE OUR OPERATIONAL IN 4622 03:07:10,040 --> 03:07:11,880 VITRO SYSTEMS BROKEN DOWN BY 4623 03:07:11,880 --> 03:07:13,680 ORGAN TYPE. 4624 03:07:13,680 --> 03:07:16,160 THIS LIST IS EVER GROWING. 4625 03:07:16,160 --> 03:07:22,400 YOU CAN SEE 2D, 3D MODELS, 4626 03:07:22,400 --> 03:07:26,120 REALTIME ANALYSIS WITH CARDIAC 4627 03:07:26,120 --> 03:07:27,640 SYSTEM, ABILITY TO LOOK AT 4628 03:07:27,640 --> 03:07:28,080 ORGANOIDS. 4629 03:07:28,080 --> 03:07:29,720 IN THE LAST FIVE YEARS WORKING 4630 03:07:29,720 --> 03:07:33,560 TO ADAPT A NUMBER OF NPS MODELS, 4631 03:07:33,560 --> 03:07:40,800 OR ORGAN ON A CHIP. 4632 03:07:40,800 --> 03:07:47,680 SO DON INGBRID SHOWCASES BREADTH 4633 03:07:47,680 --> 03:07:49,960 OF DIFFERENT ORGAN ON A CHIP 4634 03:07:49,960 --> 03:07:54,200 SYSTEMS DEVELOPED THROUGHOUT THE 4635 03:07:54,200 --> 03:07:54,400 FIELD. 4636 03:07:54,400 --> 03:07:57,080 TODAY I'LL HIGHLIGHT THREE 4637 03:07:57,080 --> 03:07:58,720 SYSTEMSE COMMERCIAL SYSTEMS 4638 03:07:58,720 --> 03:08:08,240 WE'RE USING IN HOUSE DEVELOPED 4639 03:08:08,240 --> 03:08:17,440 BY THREE COMPANIES, EMULATE, CN 4640 03:08:17,440 --> 03:08:19,240 BIO, AND TISSUSE. 4641 03:08:19,240 --> 03:08:21,680 FIRST IS A 12 WELL PLATE, WITH A 4642 03:08:21,680 --> 03:08:23,320 TRANSWELL WITH A SCAFFOLD. 4643 03:08:23,320 --> 03:08:28,920 YOU CAN INSERT YOUR PRIMARY 4644 03:08:28,920 --> 03:08:31,120 TISSUES INTO THE SCAFFOLDS, THEY 4645 03:08:31,120 --> 03:08:32,840 GENERATE 3D STRUCTURES LIKE 4646 03:08:32,840 --> 03:08:40,200 ORGANOIDS, WITHIN THERE'S A 4647 03:08:40,200 --> 03:08:40,840 UNILATERAL CIRCULATING FLOW, 4648 03:08:40,840 --> 03:08:42,720 HIGH-THROUGHPUT NATURE IS GREAT 4649 03:08:42,720 --> 03:08:44,360 FOR US, USING THIS FOR LIVER, 4650 03:08:44,360 --> 03:08:46,000 EXAMPLE OF A FIRST PASS SYSTEM 4651 03:08:46,000 --> 03:08:48,880 WE WOULD BE USING TO TEST 4652 03:08:48,880 --> 03:08:54,680 TOXICITY OF CHEMICAL AGENT PER 4653 03:08:54,680 --> 03:08:56,320 SE. 4654 03:08:56,320 --> 03:08:58,280 NEXT IS EMULATE SYSTEM. 4655 03:08:58,280 --> 03:08:59,920 HERE'S AN OVERVIEW OF THE CHIP, 4656 03:08:59,920 --> 03:09:02,320 IT'S SMALL, ABOUT THE SIZE OF A 4657 03:09:02,320 --> 03:09:06,360 FLASH DRIVE, WITH A NUMBER OF 4658 03:09:06,360 --> 03:09:07,680 COMPONENTS TO THIS CHIP. 4659 03:09:07,680 --> 03:09:09,240 I'M INCREASING THE LEVEL OF 4660 03:09:09,240 --> 03:09:12,680 COMPLEXITY WITH EACH OF THE 4661 03:09:12,680 --> 03:09:12,920 SYSTEMS. 4662 03:09:12,920 --> 03:09:15,760 WITH EMULATE, IT'S A TWO-CHANNEL 4663 03:09:15,760 --> 03:09:20,040 CHIP, TOP CHANNEL YOU WOULD SEE 4664 03:09:20,040 --> 03:09:21,080 EPITHELIUM, SEPARATED BY 4665 03:09:21,080 --> 03:09:23,000 PERMEABLE MEMBRANE, IN THE 4666 03:09:23,000 --> 03:09:26,840 BOTTOM CHANNEL YOU SEE YOUR 4667 03:09:26,840 --> 03:09:27,360 ENDOTHELIUM. 4668 03:09:27,360 --> 03:09:30,760 IT HAS VACUUM CHANNELS ON EITHER 4669 03:09:30,760 --> 03:09:33,600 SIDE USED TO IMPLEMENT STRETCH 4670 03:09:33,600 --> 03:09:34,920 WITH THE LUNG MODEL, 4671 03:09:34,920 --> 03:09:35,560 GASTROINTESTINAL MODEL, 4672 03:09:35,560 --> 03:09:43,360 CURRENTLY USING IT FOR LIVER, 4673 03:09:43,360 --> 03:09:44,560 ALVEOLUS, SMALL AIRWAY AND BRAIN 4674 03:09:44,560 --> 03:09:46,080 MODEL COMING IN SOON. 4675 03:09:46,080 --> 03:09:51,440 THIRD MODEL I'M GOING TO DISCUSS 4676 03:09:51,440 --> 03:09:55,480 IS THE TISSUSE MULTI-ORGAN CHIP. 4677 03:09:55,480 --> 03:09:57,560 HERE IS A PICTURE, DIAGRAM TO 4678 03:09:57,560 --> 03:10:00,080 THE RIGHT. 4679 03:10:00,080 --> 03:10:03,280 EACH OF THE THREE COMPARTMENTS 4680 03:10:03,280 --> 03:10:07,920 HOUSE AN ORGAN TYPE, AMENABLE TO 4681 03:10:07,920 --> 03:10:10,800 DIFFERENT ORGANS, iPSC CELLS 4682 03:10:10,800 --> 03:10:11,880 OR EVEN CELL LINES. 4683 03:10:11,880 --> 03:10:14,600 THEY ARE HOUSED IN A POLY CARBON 4684 03:10:14,600 --> 03:10:19,360 CHIP, UNDER THAT IS A PBMS 4685 03:10:19,360 --> 03:10:20,800 MICROFLUIDIC LATER PROVIDING 4686 03:10:20,800 --> 03:10:24,000 FLOW OF THE MEDIA IN THE CHIP, 4687 03:10:24,000 --> 03:10:25,400 UNDER IS MICROSCOPE SLIDE, THE 4688 03:10:25,400 --> 03:10:26,720 CHIPS ARE AMENABLE TO VIEWING 4689 03:10:26,720 --> 03:10:28,760 THE CELLS IN REAL TIME. 4690 03:10:28,760 --> 03:10:35,120 THERE'S THREE PUMPS IN THE BACK 4691 03:10:35,120 --> 03:10:43,920 OF THE CHIP3 SYSTEM 4692 03:10:43,920 --> 03:10:48,040 EXCHANGING AND PUMPING THROUGH. 4693 03:10:48,040 --> 03:10:50,360 THERE'S A CHIP4 SYSTEM, THERE 4694 03:10:50,360 --> 03:10:51,360 ARE TWO SEPARATE CIRCUITS WITHIN 4695 03:10:51,360 --> 03:10:52,440 THE CHIP. 4696 03:10:52,440 --> 03:10:55,040 THERE'S THE KIDNEY CIRCUIT AND 4697 03:10:55,040 --> 03:10:56,600 BLOOD CIRCUIT. 4698 03:10:56,600 --> 03:11:00,840 YOU HOUSE WITHIN THE CHIP 4699 03:11:00,840 --> 03:11:03,160 GLOMERULAR CELLS AND RENAL CELLS 4700 03:11:03,160 --> 03:11:04,560 KEEPING IT SEPARATE FROM THE 4701 03:11:04,560 --> 03:11:12,000 LIVER COMPONENT AND TWO OTHER 4702 03:11:12,000 --> 03:11:13,560 TISSUE TYPES FOR SKIN AND GUT 4703 03:11:13,560 --> 03:11:15,000 AND LUNG AND GUT. 4704 03:11:15,000 --> 03:11:18,920 ONE OF THE GREAT FEATURE, YOU 4705 03:11:18,920 --> 03:11:22,400 CAN DOSE AND LOOK FOR SUBSEQUENT 4706 03:11:22,400 --> 03:11:26,680 EFFECTS AT SURROUNDING ORGANS. 4707 03:11:26,680 --> 03:11:29,000 THIS MICROSCOPY IMAGE ON THE 4708 03:11:29,000 --> 03:11:32,040 RIGHT ARE HEALTHY CARDIAC 4709 03:11:32,040 --> 03:11:37,160 ORGANOIDS IN CHIP3, DOSED THESE 4710 03:11:37,160 --> 03:11:40,480 IN THE LUNG COMPARTMENT, DOSED 4711 03:11:40,480 --> 03:11:42,920 WITH HD, MUSTARD, FLOWED FOR 24 4712 03:11:42,920 --> 03:11:49,360 HOURS AND LOOKED AT EFFECTS OF 4713 03:11:49,360 --> 03:11:50,720 CARDIAC TISSUE, ORGANOIDS ARE 4714 03:11:50,720 --> 03:11:51,960 STARTING TO FALL APART. 4715 03:11:51,960 --> 03:11:54,120 YOU CAN SEE A GOOD NUMBER OF 4716 03:11:54,120 --> 03:11:55,520 CELLS WITHIN THE ORGANOID ARE 4717 03:11:55,520 --> 03:11:58,400 DEAD SO THIS IS JUST A WAY TO 4718 03:11:58,400 --> 03:12:00,200 SHOWCASE ONE OF THE NICE 4719 03:12:00,200 --> 03:12:02,000 FEATURES OF THIS SYSTEM, THAT 4720 03:12:02,000 --> 03:12:05,600 YOU CAN LOOK AT SUBSEQUENT 4721 03:12:05,600 --> 03:12:10,400 EFFECTS OF OTHER ORGANS NOT 4722 03:12:10,400 --> 03:12:11,280 DIRECTLY DOSING ON. 4723 03:12:11,280 --> 03:12:14,040 ONE OF THE ONGOING STUDIES TODAY 4724 03:12:14,040 --> 03:12:16,920 IS USE OF THIS CHIP3 SYSTEM TO 4725 03:12:16,920 --> 03:12:19,040 TEST EFFECTS OF A NUMBER OF 4726 03:12:19,040 --> 03:12:25,080 BIOLOGICAL AND CHEMICAL AGENTS, 4727 03:12:25,080 --> 03:12:27,560 ANALYZING USING DOWNSTREAM 4728 03:12:27,560 --> 03:12:29,880 MULTIOMICS ANALYSIS. 4729 03:12:29,880 --> 03:12:31,080 WE'RE SEEDING WITH CARDIAC 4730 03:12:31,080 --> 03:12:33,280 ORGANOIDS, LUNG AND SKIN TISSUE, 4731 03:12:33,280 --> 03:12:34,920 DOSING THE CHIPS DIRECTLY ON TO 4732 03:12:34,920 --> 03:12:37,560 THE LUNG AND LOOKING AT EFFECTS 4733 03:12:37,560 --> 03:12:42,560 OF ALL THREE ORGANS AFTER 4734 03:12:42,560 --> 03:12:44,040 LC-MS/MS ACQUISITION AND 4735 03:12:44,040 --> 03:12:45,680 BIOINFORMATIC IDENTIFICATION. 4736 03:12:45,680 --> 03:12:46,280 PROTEOMEICS AND METABOLOMICS, 4737 03:12:46,280 --> 03:12:48,280 THERE'S ALSO A NUMBER OF 4738 03:12:48,280 --> 03:12:51,000 DOWNSTREAM ANALYSES THAT CAN BE 4739 03:12:51,000 --> 03:12:52,520 DONE USING THIS MULTI-ORGAN 4740 03:12:52,520 --> 03:12:55,280 CHIP, GREAT FOR STAINING AND 4741 03:12:55,280 --> 03:12:58,000 IMAGING, CAN RUN ELISAS AND 4742 03:12:58,000 --> 03:12:59,320 IMMUNOASSAYS, CARDIAC ORGANOIDS 4743 03:12:59,320 --> 03:13:03,040 WE'RE LOOKING INTO TESTING THOSE 4744 03:13:03,040 --> 03:13:03,800 USING ELECTROPHYSIOLOGY METHODS, 4745 03:13:03,800 --> 03:13:07,720 AND THE LIST GOES ON WITH TYPES 4746 03:13:07,720 --> 03:13:09,840 OF ANALYSES WITH THESE CHIPS. 4747 03:13:09,840 --> 03:13:11,800 FOR THE SAKE OF TIME, I'M GOING 4748 03:13:11,800 --> 03:13:14,080 TO GIVE A SNAPSHOT OF SOME DATA 4749 03:13:14,080 --> 03:13:17,800 THAT WE'VE ACQUIRED FROM THIS 4750 03:13:17,800 --> 03:13:18,120 STUDY ALREADY. 4751 03:13:18,120 --> 03:13:20,240 HERE'S AN OVERVIEW OF THE 4752 03:13:20,240 --> 03:13:27,560 PROTEOMICS DATA FROM ONE OF OUR 4753 03:13:27,560 --> 03:13:30,080 CAR FENTANYL EXPOSURES, WITH 4754 03:13:30,080 --> 03:13:32,280 CHANGED PROTEINS, WE HAVE 4755 03:13:32,280 --> 03:13:35,160 PROTEIN FEATURES IDENTIFY WE 4756 03:13:35,160 --> 03:13:37,560 ANALYZE USING HUMAN PROTEIN 4757 03:13:37,560 --> 03:13:39,200 ATLAS DATABASE, AND THIS ALLOWS 4758 03:13:39,200 --> 03:13:42,360 US TO LOOK FOR ACTUAL 4759 03:13:42,360 --> 03:13:43,600 TISSUE-SPECIFIC DYSREGULATIONS 4760 03:13:43,600 --> 03:13:46,280 THAT ARE OCCURRING AS A RESULT 4761 03:13:46,280 --> 03:13:49,120 OF THE EXPOSURE, AS OPPOSED TO A 4762 03:13:49,120 --> 03:13:50,040 GLOBAL APPROACH, SEEING 4763 03:13:50,040 --> 03:13:51,240 DYSREGULATION THAT MIGHT BE 4764 03:13:51,240 --> 03:13:52,280 ATTRIBUTED TO OTHER ORGAN TYPES, 4765 03:13:52,280 --> 03:13:54,480 HERE WE CAN LOOK DIRECTLY AT 4766 03:13:54,480 --> 03:13:56,720 WHAT'S AFFECTING THE SKIN, THE 4767 03:13:56,720 --> 03:13:58,040 LUNG, THE CARDIAC TISSUE. 4768 03:13:58,040 --> 03:13:59,680 SO THESE VOLCANO PLOTS ARE 4769 03:13:59,680 --> 03:14:04,480 BREAKING THAT DOWN FURTHER, INTO 4770 03:14:04,480 --> 03:14:05,920 SIGNIFICANTLY DOWN AND 4771 03:14:05,920 --> 03:14:07,000 UPREGULATED PROTEINS, MAPPED IN 4772 03:14:07,000 --> 03:14:09,600 HEAT MAPS TO SHOW TOTAL NUMBER 4773 03:14:09,600 --> 03:14:11,800 OF PROTEINS IDENTIFY AND 4774 03:14:11,800 --> 03:14:13,200 DYSREGULATED. 4775 03:14:13,200 --> 03:14:16,640 I'M GOING TO HIGHLIGHT THESE TWO 4776 03:14:16,640 --> 03:14:18,680 GRAPHS HERE SHOWING RELATIVE 4777 03:14:18,680 --> 03:14:24,200 PROTEIN ABUNDANCE COMPARED TO 4778 03:14:24,200 --> 03:14:27,360 THE UNTREATED CARDIAC ORGANOIDS 4779 03:14:27,360 --> 03:14:29,760 IN THIS CASE, THESE TWO PROTEINS 4780 03:14:29,760 --> 03:14:31,800 ARE PIVOTAL IN CALCIUM HANDLING 4781 03:14:31,800 --> 03:14:33,160 FOR THE CELLS. 4782 03:14:33,160 --> 03:14:37,120 ONE THING I DIDN'T MENTION WITH 4783 03:14:37,120 --> 03:14:38,360 THE STUDY, SPECIFICALLY 4784 03:14:38,360 --> 03:14:40,160 INTERESTED IN LOOKING AT 4785 03:14:40,160 --> 03:14:41,760 PHYSIOLOGICAL EFFECTS THAT ARE 4786 03:14:41,760 --> 03:14:44,360 OCCURRING AS A RESULT OF 4787 03:14:44,360 --> 03:14:52,440 EXPOSURE TO THESE AGENTS, FUNDED 4788 03:14:52,440 --> 03:14:54,320 BY DITRA INTERESTED IN 4789 03:14:54,320 --> 03:14:56,720 BIOMARKERS TO DEVELOP WEARABLE 4790 03:14:56,720 --> 03:14:57,080 DEVICES. 4791 03:14:57,080 --> 03:14:57,880 PROTEIN DYSREGULATIONS STOOD OUT 4792 03:14:57,880 --> 03:15:00,560 TO US BECAUSE OF THE CALCIUM 4793 03:15:00,560 --> 03:15:02,640 HANDLING IMPLICATION, AND THIS 4794 03:15:02,640 --> 03:15:05,160 CAN BE DIRECTLY CORRELATED TO 4795 03:15:05,160 --> 03:15:07,440 ARRHYTHMIA WITHIN THE HEART. 4796 03:15:07,440 --> 03:15:09,400 WE'RE LOOKING AT SAME TIMES OF 4797 03:15:09,400 --> 03:15:11,280 DYSREGULATIONS IN THE LUNG AND 4798 03:15:11,280 --> 03:15:13,400 SKIN, SKIN YOU'RE SEEING A LOT 4799 03:15:13,400 --> 03:15:15,200 OF PROTEINS INVOLVED IN THE 4800 03:15:15,200 --> 03:15:17,200 INTEGRITY OF THE SKIN TISSUE 4801 03:15:17,200 --> 03:15:18,720 BEING AFFECTED AND THERE'S A LOT 4802 03:15:18,720 --> 03:15:23,000 OF LUNG CELL SIGNALING THAT'S 4803 03:15:23,000 --> 03:15:24,280 BEING AFFECTED AS WELL. 4804 03:15:24,280 --> 03:15:31,880 WE ALSO LOOKED AT EXPOSURES TO 4805 03:15:31,880 --> 03:15:32,720 THE TOXIN STAPHYLOCOCCUS 4806 03:15:32,720 --> 03:15:34,360 ENTEROTOXIN B, THE NUMBER OF 4807 03:15:34,360 --> 03:15:35,800 PROTEINS FOUND AND SIGNIFICANTLY 4808 03:15:35,800 --> 03:15:37,880 CHANGED AS WELL AS VOLCANO PLOTS 4809 03:15:37,880 --> 03:15:40,160 FOR DIFFERENT ORGANS WE LOOKED 4810 03:15:40,160 --> 03:15:41,480 INTO AND HEAT MAPS. 4811 03:15:41,480 --> 03:15:45,560 SO WHEN WE WERE ANALYZING THIS 4812 03:15:45,560 --> 03:15:47,560 DATA, THESE DATA, ONE OF THE 4813 03:15:47,560 --> 03:15:48,800 PROTEIN DYSREGULATIONS THAT 4814 03:15:48,800 --> 03:15:56,040 STOOD OUT TO OUR 4815 03:15:56,040 --> 03:15:58,560 BIOINFORMITICIAN WAS THIS. 4816 03:15:58,560 --> 03:16:00,640 IT STAND FOR SMALL 4817 03:16:00,640 --> 03:16:02,680 UBIQUITIN-LIKE MODIFYING 4818 03:16:02,680 --> 03:16:04,680 PROTEIN, SUMO. 4819 03:16:04,680 --> 03:16:06,880 LIKE UBIQUITIN THIS MOLECULE 4820 03:16:06,880 --> 03:16:09,800 REGULATES A NUMBER OF CELLULAR 4821 03:16:09,800 --> 03:16:11,080 RESPONSES, CELLULAR PATHWAYS AND 4822 03:16:11,080 --> 03:16:14,440 FACTORS WHICH ARE SHOWN AT THE 4823 03:16:14,440 --> 03:16:16,640 BOTTOM OF THE SLIDE. 4824 03:16:16,640 --> 03:16:18,240 USUALLY REPRESSION A LOT OF 4825 03:16:18,240 --> 03:16:21,640 THESE DIFFERENT PROCESSES. 4826 03:16:21,640 --> 03:16:23,000 THIS ENZYME IS ABSOLUTELY 4827 03:16:23,000 --> 03:16:26,600 REQUIRED FOR SIMULATION TO 4828 03:16:26,600 --> 03:16:26,800 OCCUR. 4829 03:16:26,800 --> 03:16:29,200 WITHOUT THAT SIMULATIONS ARE 4830 03:16:29,200 --> 03:16:29,640 NON-OCCURRING. 4831 03:16:29,640 --> 03:16:32,160 FROM THERE WE LOOKED INTO EACH 4832 03:16:32,160 --> 03:16:33,600 OF THESE INDIVIDUAL PROCESSES, 4833 03:16:33,600 --> 03:16:35,120 PROTEINS ASSOCIATED WITH THEM 4834 03:16:35,120 --> 03:16:36,760 AND LOOKED FOR FURTHER 4835 03:16:36,760 --> 03:16:37,720 DYSREGULATION TO TEASE APART 4836 03:16:37,720 --> 03:16:40,880 WHAT'S GOING ON WITH THE 4837 03:16:40,880 --> 03:16:41,600 SUBEXPOSURE. 4838 03:16:41,600 --> 03:16:43,640 AND WHAT WE FOUND WAS 4839 03:16:43,640 --> 03:16:44,920 DYSREGULATION OCCURRING IN THIS 4840 03:16:44,920 --> 03:16:45,840 PROTEIN PHASE 1. 4841 03:16:45,840 --> 03:16:50,040 SO THIS IS AN ADAPTIVE PROTEIN, 4842 03:16:50,040 --> 03:16:54,680 INVOLVED IN PERIPHERAL DIVISION 4843 03:16:54,680 --> 03:16:58,840 OF MITOCHONDRIA, SO 4844 03:16:58,840 --> 03:17:00,480 MITOCHONDRIAL FISSION, IMPORTANT 4845 03:17:00,480 --> 03:17:02,600 WHEN THEY UNDERGO DEVELOP 4846 03:17:02,600 --> 03:17:04,480 STRESSES, SO WHEN STRESSES 4847 03:17:04,480 --> 03:17:07,720 OCCUR, IN ORDER TO MAKE NEW 4848 03:17:07,720 --> 03:17:09,240 MITOCHONDRIA THEY HAVE TO FUSE 4849 03:17:09,240 --> 03:17:10,680 SICK MITOCHONDRIA OR DIVIDE 4850 03:17:10,680 --> 03:17:12,280 HEALTHY MITOCHONDRIA TO KEEP THE 4851 03:17:12,280 --> 03:17:16,920 ENERGETICS OF THE CELL GOING. 4852 03:17:16,920 --> 03:17:19,640 WE LOOKED FURTHER AND JUST 4853 03:17:19,640 --> 03:17:20,320 SEARCHED FOR MITOCHONDRIAL 4854 03:17:20,320 --> 03:17:22,800 DYSREGULATIONS IN EACH OF THE 4855 03:17:22,800 --> 03:17:24,680 THREE DIFFERENT TISSUE TIMES 4856 03:17:24,680 --> 03:17:29,600 THAT WE TESTED, WITH OUR 4857 03:17:29,600 --> 03:17:30,800 ENRICHMENT MAPPING SHOWING 4858 03:17:30,800 --> 03:17:32,760 DYSREGULATION IN PROCESSES AND 4859 03:17:32,760 --> 03:17:35,480 HIGHLIGHTED IN PURPLE WERE ALL 4860 03:17:35,480 --> 03:17:36,240 THE MITOCHONDRIAL ASSOCIATED 4861 03:17:36,240 --> 03:17:38,120 DYSREGULATIONS IN EACH OF THE 4862 03:17:38,120 --> 03:17:40,000 THREE ORGAN TYPES SO WE KNEW 4863 03:17:40,000 --> 03:17:44,680 SOMETHING WAS REALLY HAPPENING 4864 03:17:44,680 --> 03:17:45,280 WITH MITOCHONDRIA. 4865 03:17:45,280 --> 03:17:47,680 WHEN YOU BREAK THAT DOWN INTO 4866 03:17:47,680 --> 03:17:52,920 TOP DYSFUNCTIONS AS SHOWN IN THE 4867 03:17:52,920 --> 03:17:54,800 ENRICHMENT MAPPING YOU SEE A LOT 4868 03:17:54,800 --> 03:17:56,560 OF RESPONSES ASSOCIATED WITH 4869 03:17:56,560 --> 03:17:59,160 SIMULATION, SO THREE I'VE 4870 03:17:59,160 --> 03:18:00,480 HIGHLIGHTED DOWNREGULATED, THEY 4871 03:18:00,480 --> 03:18:02,600 ARE ALL INVOLVED IN SIMULATION. 4872 03:18:02,600 --> 03:18:06,360 AND THEN AT THE TOP THE 4873 03:18:06,360 --> 03:18:07,200 UPREGULATED PROCESSES WOULD BE 4874 03:18:07,200 --> 03:18:08,280 POTENTIAL BIOMARKERS THAT WE 4875 03:18:08,280 --> 03:18:14,880 COULD GO AFTER THAT WERE 4876 03:18:14,880 --> 03:18:18,880 ASSOCIATED WITH SUBEXPOSURE. 4877 03:18:18,880 --> 03:18:20,720 SO PENTOSE PHOSPATE WOULD 4878 03:18:20,720 --> 03:18:23,720 INDICATE SWITCH TO ANAEROBIC 4879 03:18:23,720 --> 03:18:26,720 RESPIRATION, LOOKING AT LACTIC 4880 03:18:26,720 --> 03:18:28,240 ACID BIOMARKERS, BUILDUP, WE 4881 03:18:28,240 --> 03:18:31,040 WOULD LOOK AT CALCIUM HANDLING, 4882 03:18:31,040 --> 03:18:37,400 DUE TO MITOCHONDRIA BEING SICK. 4883 03:18:37,400 --> 03:18:38,360 VASOPRESENT SYNTHESIS 4884 03:18:38,360 --> 03:18:40,360 UPREGULATED, INDICATOR THERE WAS 4885 03:18:40,360 --> 03:18:41,640 EFFECT WITH BLOOD PRESSURE, AND 4886 03:18:41,640 --> 03:18:45,800 WE CAN LOOK AT ADRENALINE AS A 4887 03:18:45,800 --> 03:18:47,320 READOUT, ATP ANOTHER GOOD THING 4888 03:18:47,320 --> 03:18:49,200 TO LOOK INTO AND THERE'S GOING 4889 03:18:49,200 --> 03:18:53,680 TO BE A FOLLOW-ON STUDY 4890 03:18:53,680 --> 03:18:54,680 ADDRESSING THESE MITOCHONDRIAL 4891 03:18:54,680 --> 03:18:55,000 DYSFUNCTIONS. 4892 03:18:55,000 --> 03:18:57,080 SO NOW I WANT TO GET INTO SOME 4893 03:18:57,080 --> 03:19:01,120 OF THE OTHER EFFORTS USING 4894 03:19:01,120 --> 03:19:02,560 MULTI-ORGAN CHIP SYSTEMS, SHOWN 4895 03:19:02,560 --> 03:19:07,440 HERE ON THIS SLIDE IS AN AEROSOL 4896 03:19:07,440 --> 03:19:09,840 DELIVERY SYSTEM, DEVELOPED BY 4897 03:19:09,840 --> 03:19:12,800 PHILIP MORRIS INTERNATIONAL. 4898 03:19:12,800 --> 03:19:14,800 THIS RECAPITULATES THE ENTIRE 4899 03:19:14,800 --> 03:19:17,000 RESPIRATORY TRACT. 4900 03:19:17,000 --> 03:19:18,720 THERE'S THREE SEPARATE MODULES 4901 03:19:18,720 --> 03:19:21,040 WITHIN THIS AEROSOL DELIVERY 4902 03:19:21,040 --> 03:19:22,800 SYSTEM, ORAL MODULE, LUNG 4903 03:19:22,800 --> 03:19:24,520 MODULE, AIRWAY MODEL. 4904 03:19:24,520 --> 03:19:30,920 YOU CAN ACTUALLY LOOK AT THE MA 4905 03:19:30,920 --> 03:19:36,480 -- MATURATION, THEY ADAPTED 4906 03:19:36,480 --> 03:19:41,160 CHANGES IN THE HUMAN AIRWAY, 4907 03:19:41,160 --> 03:19:45,680 THIS INHALES MODEL HAS RECENTLY 4908 03:19:45,680 --> 03:19:52,240 BEEN ADAPTED TO SMALL T ORGAN 4909 03:19:52,240 --> 03:19:53,280 CHIP, WORKING WITH TISSUSE SO 4910 03:19:53,280 --> 03:19:55,560 YOU CAN LOOK AT THE DIFFERENT 4911 03:19:55,560 --> 03:19:57,960 EFFECTS AT DIFFERENT PARTS IN 4912 03:19:57,960 --> 03:19:59,920 THE AIR WAY, TAKE TISSUES OUT 4913 03:19:59,920 --> 03:20:01,880 AND DO DOWNSTREAM ANALYSIS. 4914 03:20:01,880 --> 03:20:03,360 WE'RE GETTING THIS SYSTEM IN 4915 03:20:03,360 --> 03:20:06,120 HOUSE AT THE END OF THE SUMMER, 4916 03:20:06,120 --> 03:20:07,440 BETA TESTING FOR THEM TO SEE HOW 4917 03:20:07,440 --> 03:20:13,960 IT WORKS WITH THE CHIPS. 4918 03:20:13,960 --> 03:20:16,240 A NUMBER OF OTHER MOC PROJECTS 4919 03:20:16,240 --> 03:20:19,400 IN THE WORKS, FIRST WOULD BE 4920 03:20:19,400 --> 03:20:23,040 RECREATING ADME MOC, AS I 4921 03:20:23,040 --> 03:20:26,440 MENTIONED THE CHIP4 HAS TWO 4922 03:20:26,440 --> 03:20:27,440 CIRCUITS, KIDNEY AND BLOOD. 4923 03:20:27,440 --> 03:20:31,480 WE CAN LOOK AT ABSORPTION, 4924 03:20:31,480 --> 03:20:32,480 DISTRIBUTION, METABOLISM, 4925 03:20:32,480 --> 03:20:34,680 EXCRETION, WITHIN THESE CHIPS, 4926 03:20:34,680 --> 03:20:36,720 IN THIS CASE WITH 4927 03:20:36,720 --> 03:20:37,880 WELL-CHARACTERIZED ANTIBIOTICS. 4928 03:20:37,880 --> 03:20:40,440 SO THAT'S ONE COMPONENT OF IT. 4929 03:20:40,440 --> 03:20:42,760 WE'RE TRYING TO ESTABLISH 4930 03:20:42,760 --> 03:20:44,960 INFECTION MODEL USING THESE 4931 03:20:44,960 --> 03:20:46,360 CHIPS, ADD A DRUG, LOOK AT 4932 03:20:46,360 --> 03:20:51,600 EFFICACY OF DRUGS WITHIN THE 4933 03:20:51,600 --> 03:20:52,720 CONTEXT OF THE TISS-USE CHIP AND 4934 03:20:52,720 --> 03:20:54,960 COMPARE WITH DATA TO SEE 4935 03:20:54,960 --> 03:20:57,040 TRANSLATIONAL CAPABILITY OF THIS 4936 03:20:57,040 --> 03:20:58,600 CHIP FOR THAT PURPOSE. 4937 03:20:58,600 --> 03:21:02,240 WE'RE ALSO WORKING TO LOOK AT 4938 03:21:02,240 --> 03:21:07,040 VOCs EMITTED FROM THE LUNG 4939 03:21:07,040 --> 03:21:07,880 COMPARTMENT OF THE CHIP, WHAT 4940 03:21:07,880 --> 03:21:10,840 THEY HAVE BECOME GOOD AT IS 4941 03:21:10,840 --> 03:21:13,320 BREATH MASS SPEC, SO THEY ARE 4942 03:21:13,320 --> 03:21:14,760 GENERATING PROFILES OF HUMAN 4943 03:21:14,760 --> 03:21:16,600 BREATH AND VOCs THAT THEY CAN 4944 03:21:16,600 --> 03:21:17,960 DETECT FROM NORMAL HUMAN BREATH 4945 03:21:17,960 --> 03:21:21,120 AND OUR AIM IS TO COLLECT VOCs 4946 03:21:21,120 --> 03:21:22,320 FROM THE MULTI-ORGAN CHIP AND 4947 03:21:22,320 --> 03:21:23,320 SEE HOW THAT COMPARES TO THE 4948 03:21:23,320 --> 03:21:26,040 DATA THAT THEY HAVE ALREADY 4949 03:21:26,040 --> 03:21:28,360 GENERATED, AGAIN LOOKING AT 4950 03:21:28,360 --> 03:21:30,000 TRANSLATIONAL CAPABILITY OF 4951 03:21:30,000 --> 03:21:31,040 THESE CHIPS. 4952 03:21:31,040 --> 03:21:33,040 FINALLY, OUR LAST EFFORT THAT 4953 03:21:33,040 --> 03:21:36,760 WE'RE CURRENTLY WORKING ON IS TO 4954 03:21:36,760 --> 03:21:38,160 CREATE A DIAGNOSTIC TRANSLATION 4955 03:21:38,160 --> 03:21:40,480 CHIP, SO WE'RE USING THE CHIP3 4956 03:21:40,480 --> 03:21:42,480 SYSTEM FOR THIS, AND WE ARE 4957 03:21:42,480 --> 03:21:45,720 PICKING DRUGS THAT ARE 4958 03:21:45,720 --> 03:21:47,040 WELL-CHARACTERIZED THAT HAVE 4959 03:21:47,040 --> 03:21:48,480 GONE THROUGH CLINICAL TRIALS AND 4960 03:21:48,480 --> 03:21:52,960 WE HAVE OMICS DATA ON THOSE 4961 03:21:52,960 --> 03:21:53,160 DRUGS. 4962 03:21:53,160 --> 03:21:55,480 AND ADD THOSE TO THE CHIPS, 4963 03:21:55,480 --> 03:21:57,280 COLLECT THOSE SAME OMICS AND SEE 4964 03:21:57,280 --> 03:22:02,200 HOW IT COMPARES TO THE HUMAN 4965 03:22:02,200 --> 03:22:04,640 DATA. 4966 03:22:04,640 --> 03:22:06,200 MY LAST SLIDE IS JUST AGAIN AN 4967 03:22:06,200 --> 03:22:07,840 OVERVIEW OF ALL OF OUR 4968 03:22:07,840 --> 03:22:09,360 OPERATIONAL SYSTEMS THAT WE HAVE 4969 03:22:09,360 --> 03:22:11,240 IN HOUSE AND WHAT WE HAVE IN 4970 03:22:11,240 --> 03:22:11,560 DEVELOPMENT. 4971 03:22:11,560 --> 03:22:13,080 ONE THING I DIDN'T REALLY TOUCH 4972 03:22:13,080 --> 03:22:15,600 ON IS MORE OF THE AIR SOME 4973 03:22:15,600 --> 03:22:20,120 EXPOSURE EFFORTS THAT WE HAVE IN 4974 03:22:20,120 --> 03:22:23,960 PLACE, ONE OF THE MAJOR 4975 03:22:23,960 --> 03:22:25,400 DRAWBACKS THEY ARE NOT TUNED FOR 4976 03:22:25,400 --> 03:22:31,160 AIL SORE -- AEROSOL EXPOSURES, 4977 03:22:31,160 --> 03:22:32,680 IT'S HARD TO EXPOSE THEM. 4978 03:22:32,680 --> 03:22:36,840 THEY ARE CLOSE SYSTEMS. 4979 03:22:36,840 --> 03:22:39,440 WE'RE WORKING TO DESIGN OUR OWN 4980 03:22:39,440 --> 03:22:43,400 CHIP SYSTEM AND AEROSOL DELIVERY 4981 03:22:43,400 --> 03:22:45,280 SETUPS THAT WE'RE 3D PRINTING IN 4982 03:22:45,280 --> 03:22:47,320 HOUSE TO DO THOSE AEROSOL 4983 03:22:47,320 --> 03:22:51,000 EXPOSURES. 4984 03:22:51,000 --> 03:22:51,360 4985 03:22:51,360 --> 03:22:53,240 WITH THAT, I WOULD LIKE TO THANK 4986 03:22:53,240 --> 03:22:55,520 MY TEAM MEMBERS FROM THE 4987 03:22:55,520 --> 03:22:57,400 MOLECULAR TOXICOLOGY BRANCH AS 4988 03:22:57,400 --> 03:22:58,600 WELL AS BIODEFENSE BRANCH SO A 4989 03:22:58,600 --> 03:23:00,680 NUMBER OF THESE GUYS ARE WORKING 4990 03:23:00,680 --> 03:23:02,640 ON THE CHIP EFFORTS THEMSELVES 4991 03:23:02,640 --> 03:23:06,200 OR GOING INTO THE BSL3 AND DOING 4992 03:23:06,200 --> 03:23:07,600 SELECT AGENT EXPOSURES AND WITH 4993 03:23:07,600 --> 03:23:11,040 THAT I WILL TAKE ANY QUESTIONS. 4994 03:23:11,040 --> 03:23:13,040 [APPLAUSE] 4995 03:23:13,040 --> 03:23:17,560 4996 03:23:17,560 --> 03:23:22,720 >> THANK YOU, TYLER. 4997 03:23:22,720 --> 03:23:24,120 I HAVE ONE QUESTION. 4998 03:23:24,120 --> 03:23:25,920 IN TERMS OF LOOKING AT THE 4999 03:23:25,920 --> 03:23:28,160 AEROSOL EXPOSURE SYSTEMS ARE YOU 5000 03:23:28,160 --> 03:23:29,800 INCORPORATING CONSIDERATION OF 5001 03:23:29,800 --> 03:23:33,240 SYSTEMS THAT WOULD ALLOW 5002 03:23:33,240 --> 03:23:34,080 EXPOSURES OF DEFINED MIXTURES? 5003 03:23:34,080 --> 03:23:34,880 >> YES. 5004 03:23:34,880 --> 03:23:36,200 SO THAT IS DEFINITELY SOMETHING 5005 03:23:36,200 --> 03:23:37,720 IN THE WORKS, SOMETHING WE'VE 5006 03:23:37,720 --> 03:23:39,040 BEEN TALKING ABOUT FOR YEARS 5007 03:23:39,040 --> 03:23:39,200 NOW. 5008 03:23:39,200 --> 03:23:42,720 NOT EVEN IN THE CONTEXT OF ORGAN 5009 03:23:42,720 --> 03:23:51,360 ON A CHIP BUT STARTING TO CREATE 5010 03:23:51,360 --> 03:23:52,960 MATRICES AND TESTING IN VIVO OR 5011 03:23:52,960 --> 03:23:53,240 ZEBRAFISH. 5012 03:23:53,240 --> 03:23:54,880 >> DO YOU HAVE PLATFORMS YOU'RE 5013 03:23:54,880 --> 03:23:56,400 DOING THAT WITH NOW OR IS THAT 5014 03:23:56,400 --> 03:23:58,920 STILL SORT OF IN THE DEVELOPMENT 5015 03:23:58,920 --> 03:23:59,120 STAGE? 5016 03:23:59,120 --> 03:24:01,200 >> YEAH, THAT'S STILL IN THE 5017 03:24:01,200 --> 03:24:02,680 DEVELOPMENT STAGE. 5018 03:24:02,680 --> 03:24:06,160 I THINK THE REAL GOAL WOULD BE 5019 03:24:06,160 --> 03:24:08,360 DOING SOMETHING LIKE THAT WITH 5020 03:24:08,360 --> 03:24:11,200 THE INHALE SYSTEM BUT WE'RE JUST 5021 03:24:11,200 --> 03:24:12,400 BETA TESTING WITH INNOCUOUS 5022 03:24:12,400 --> 03:24:15,600 MATERIAL TO SHOW ITS METTLE. 5023 03:24:15,600 --> 03:24:15,840 >> OKAY. 5024 03:24:15,840 --> 03:24:16,040 GREAT. 5025 03:24:16,040 --> 03:24:17,560 THANK YOU SO MUCH. 5026 03:24:17,560 --> 03:24:26,960 ANY OTHER QUESTIONS IN THE ROOM 5027 03:24:26,960 --> 03:24:29,360 YEAH, ANOTHER QUESTION HERE. 5028 03:24:29,360 --> 03:24:29,720 >> GREAT TALK. 5029 03:24:29,720 --> 03:24:30,120 THANK YOU. 5030 03:24:30,120 --> 03:24:33,520 DO YOU FLOW IF THE ORGAN A CHIP 5031 03:24:33,520 --> 03:24:39,120 SYSTEMS ARE AMENABLE TO LARGE 5032 03:24:39,120 --> 03:24:41,200 MOLECULE OR CELL-BASED THERAPY 5033 03:24:41,200 --> 03:24:41,440 TESTING? 5034 03:24:41,440 --> 03:24:44,800 >> SO, LARGE MOLECULE TESTING 5035 03:24:44,800 --> 03:24:46,720 WOULD DEFINITELY BE DOABLE WITH 5036 03:24:46,720 --> 03:24:52,040 SOMETHING LIKE THE CN BIOOR 5037 03:24:52,040 --> 03:24:53,480 TISS-USE SYSTEM. 5038 03:24:53,480 --> 03:24:56,240 FOR EMULATE, IT DEPENDS HOW BIG 5039 03:24:56,240 --> 03:24:57,440 YOU'RE TALKING. 5040 03:24:57,440 --> 03:24:58,640 YEAH, SOME COMMERCIAL SYSTEMS 5041 03:24:58,640 --> 03:25:02,000 WOULD BE AMENABLE TO THAT. 5042 03:25:02,000 --> 03:25:06,760 WHAT WAS THE SECOND QUESTION? 5043 03:25:06,760 --> 03:25:11,000 >> CELL THERAPY. 5044 03:25:11,000 --> 03:25:12,840 >>CELL THERAPY. 5045 03:25:12,840 --> 03:25:16,000 ARE YOU TALKING ABOUT 5046 03:25:16,000 --> 03:25:21,280 INTEGRATING GENETICALLY MODIFIED 5047 03:25:21,280 --> 03:25:26,320 LINES INTO THE SYSTEM? 5048 03:25:26,320 --> 03:25:29,040 >> SO ACTUALLY YES, 5049 03:25:29,040 --> 03:25:29,880 SPECIFICALLY CAR Ts. 5050 03:25:29,880 --> 03:25:31,120 JUST TO SEE, YOU KNOW, IF YOU 5051 03:25:31,120 --> 03:25:32,680 COULD RUN IT THROUGH THERE IN 5052 03:25:32,680 --> 03:25:34,400 THAT SYSTEM AND SEE HOW THEY 5053 03:25:34,400 --> 03:25:37,360 BIND AND DO THEIR THING. 5054 03:25:37,360 --> 03:25:39,200 >> I MEAN, THAT'S NOT SOMETHING 5055 03:25:39,200 --> 03:25:40,720 WE'VE LOOKED INTO. 5056 03:25:40,720 --> 03:25:42,800 YOU KNOW, OUR GROUP, THAT'S OUT 5057 03:25:42,800 --> 03:25:44,480 OF OUR PURVIEW BUT I DON'T SEE 5058 03:25:44,480 --> 03:25:47,320 WHY YOU COULDN'T. 5059 03:25:47,320 --> 03:25:47,440 5060 03:25:47,440 --> 03:25:50,160 >> I THINK OUR NEXT PRESENTER 5061 03:25:50,160 --> 03:25:52,200 DR. DAN TAGLE MAY HAVE SOME 5062 03:25:52,200 --> 03:25:55,480 INFORMED PERSPECTIVE ON THAT 5063 03:25:55,480 --> 03:25:56,840 QUESTION AS WELL. 5064 03:25:56,840 --> 03:25:58,800 ANY OTHER QUESTIONS ONLINE? 5065 03:25:58,800 --> 03:26:00,080 OKAY. 5066 03:26:00,080 --> 03:26:03,680 AND JUST TO NOTE, WE SEE DR. 5067 03:26:03,680 --> 03:26:04,080 VALERIO REJOINED. 5068 03:26:04,080 --> 03:26:07,000 AT THE END AFTER THIS LAST 5069 03:26:07,000 --> 03:26:08,200 PRESENTATION WE'LL COME BACK TO 5070 03:26:08,200 --> 03:26:09,720 A FINAL OPEN DISCUSSION SECTION 5071 03:26:09,720 --> 03:26:11,720 WHERE WE CAN REVISIT ANY OF THE 5072 03:26:11,720 --> 03:26:13,360 QUESTIONS WE DIDN'T DO, GENERAL 5073 03:26:13,360 --> 03:26:15,760 COMMENTS THAT HAVE COME FROM OUR 5074 03:26:15,760 --> 03:26:17,040 ONLINE PARTICIPANTS, ET CETERA. 5075 03:26:17,040 --> 03:26:20,360 SO LET ME JUST TRY AND PULL UP 5076 03:26:20,360 --> 03:26:30,600 DAN'S SLIDES. 5077 03:26:40,240 --> 03:26:41,480 IT ONLY TOOK THE ENTIRE TWO DAYS 5078 03:26:41,480 --> 03:26:43,960 FOR ME TO FIGURE OUT HOW TO WORK 5079 03:26:43,960 --> 03:26:46,600 THIS SYSTEM. 5080 03:26:46,600 --> 03:26:47,560 HERE WE GO, DAN. 5081 03:26:47,560 --> 03:26:49,040 >> THANK YOU. 5082 03:26:49,040 --> 03:26:51,440 ALL IN PREPARATION FOR ME. 5083 03:26:51,440 --> 03:26:53,600 GOOD AFTERNOON, TO THOSE IN 5084 03:26:53,600 --> 03:26:54,360 PERSON AND ATTENDING ONLINE, A 5085 03:26:54,360 --> 03:26:55,920 PLEASURE TO BE HERE. 5086 03:26:55,920 --> 03:26:58,760 THANK YOU, NICOLE, FOR THE KIND 5087 03:26:58,760 --> 03:26:59,520 INVITATION. 5088 03:26:59,520 --> 03:27:01,720 JUST TO BRIEFLY ANSWER THE LAST 5089 03:27:01,720 --> 03:27:04,880 QUESTION, WE HAVE HAD EXPERIENCE 5090 03:27:04,880 --> 03:27:08,400 IN OUR FUNDED PROJECTS IN TERMS 5091 03:27:08,400 --> 03:27:10,680 OF MACROMOLECULES OF VACCINES, 5092 03:27:10,680 --> 03:27:14,520 BIOLOGICS, AND AS WELL AS CELL 5093 03:27:14,520 --> 03:27:15,840 THERAPIES. 5094 03:27:15,840 --> 03:27:19,760 SOMATIC CELL GENE EDITING AND 5095 03:27:19,760 --> 03:27:21,640 EXOSOME BASED FOR EVALUATION OF 5096 03:27:21,640 --> 03:27:23,160 EFFICACY AND BIODISTRIBUTION. 5097 03:27:23,160 --> 03:27:25,920 I WON'T BE ABLE TO TOUCH BASE ON 5098 03:27:25,920 --> 03:27:27,360 THAT IN THIS PRESENTATION. 5099 03:27:27,360 --> 03:27:30,080 MY TALK TODAY IS GOING TO BE 5100 03:27:30,080 --> 03:27:32,920 MORE OF A LARGE OVERVIEW OF 5101 03:27:32,920 --> 03:27:39,080 WHAT'S BEEN GOING ON IN TERMS OF 5102 03:27:39,080 --> 03:27:40,600 DEVELOPING TISSUE CHIPS OR 5103 03:27:40,600 --> 03:27:42,040 MICROPHYSIOLOGIC SYSTEMS 5104 03:27:42,040 --> 03:27:43,680 PRIMARILY IN CONTEXT OF DRUG 5105 03:27:43,680 --> 03:27:44,840 DEVELOP AM. 5106 03:27:44,840 --> 03:27:47,800 I COME FROM NATIONAL CENTER FOR 5107 03:27:47,800 --> 03:27:48,280 ADVANCING TRANSLATIONAL 5108 03:27:48,280 --> 03:27:48,560 SCIENCES. 5109 03:27:48,560 --> 03:27:50,440 >> I'M JUST GOING TO MOVE -- I 5110 03:27:50,440 --> 03:27:51,760 THOUGHT I FIGURED IT OUT. 5111 03:27:51,760 --> 03:27:53,400 LET ME MOVE THE MEETING CONTROLS 5112 03:27:53,400 --> 03:27:55,800 SO EVERYONE CAN SEE THE FULL 5113 03:27:55,800 --> 03:27:59,760 CONTENT OF YOUR SLIDES. 5114 03:27:59,760 --> 03:28:00,920 THERE WE GO. 5115 03:28:00,920 --> 03:28:02,360 >> THANK YOU, NICOLE. 5116 03:28:02,360 --> 03:28:05,000 YEAH, NATIONAL CENTER FOR 5117 03:28:05,000 --> 03:28:06,200 ADVANCING TRANSLATIONAL SCIENCES 5118 03:28:06,200 --> 03:28:08,720 IS WITHIN THE NIH. 5119 03:28:08,720 --> 03:28:12,120 AND WE HAVE OUR MISSION, OUR 5120 03:28:12,120 --> 03:28:14,760 GOAL, TO ADDRESS LONGSTANDING 5121 03:28:14,760 --> 03:28:20,080 BOTTLENECKS OR WHAT WE CALL ROAD 5122 03:28:20,080 --> 03:28:20,680 BLOCKS INTO TRANSLATIONAL 5123 03:28:20,680 --> 03:28:21,840 PIPELINE, SOME IN INDUSTRY CALL 5124 03:28:21,840 --> 03:28:25,800 IT THE VALLEY OF DEATH. 5125 03:28:25,800 --> 03:28:28,200 IN THIS PARTICULAR EXAMPLE, IN 5126 03:28:28,200 --> 03:28:30,160 TERMS OF RELATIONSHIP TO 5127 03:28:30,160 --> 03:28:31,800 DEVELOPING TISSUE CHIPS, THE 5128 03:28:31,800 --> 03:28:32,480 TRANSLATIONAL PROBLEMS THAT 5129 03:28:32,480 --> 03:28:34,480 WE'RE TRYING TO SOLVE IS 5130 03:28:34,480 --> 03:28:38,680 PRIMARILY LOOKING AT SMALL 5131 03:28:38,680 --> 03:28:40,560 MOLECULES, 90% FAIL IN THE 5132 03:28:40,560 --> 03:28:43,720 CONTEXT OF DRUG DEVELOPMENT FROM 5133 03:28:43,720 --> 03:28:45,040 EARLY DISCOVERY, PRE-CLINICAL, 5134 03:28:45,040 --> 03:28:46,560 TO CLINICAL TRIALS, TAKES AN 5135 03:28:46,560 --> 03:28:54,160 AVERAGE OF 10 TO 15 YEARS TO 5136 03:28:54,160 --> 03:28:56,760 COME TO MARKET, $2.6 BILLION PER 5137 03:28:56,760 --> 03:28:57,520 MARKET-APPROVED DRUG. 5138 03:28:57,520 --> 03:28:59,600 SO, THOSE IN THE INDUSTRY IN THE 5139 03:28:59,600 --> 03:29:02,360 PHARMA INDUSTRY HAVE LONG LOOKED 5140 03:29:02,360 --> 03:29:04,960 AT WHERE THE INEFFICIENCIES ARE, 5141 03:29:04,960 --> 03:29:07,560 AND THEY HAVE LOOKED AND POINTED 5142 03:29:07,560 --> 03:29:09,720 TO INSUFFICIENT TOOLS AND 5143 03:29:09,720 --> 03:29:11,680 TECHNOLOGIES THAT ARE CERTAINLY 5144 03:29:11,680 --> 03:29:14,400 NOT CAPABLE OF ACCURATELY 5145 03:29:14,400 --> 03:29:16,400 PREDICTING HUMAN SAFETY AS WELL 5146 03:29:16,400 --> 03:29:18,840 AS EFFICACY OF CANDIDATE DRUGS. 5147 03:29:18,840 --> 03:29:21,840 SO OUR SOLUTION IN TERMS OF 5148 03:29:21,840 --> 03:29:24,920 NCATS SOLUTION IS TO COME UP 5149 03:29:24,920 --> 03:29:26,040 WITH BETTER PREDICTIVE TOOLS, 5150 03:29:26,040 --> 03:29:27,880 AND THAT ARE MORE HUMAN BASED 5151 03:29:27,880 --> 03:29:29,520 BECAUSE THE ANIMAL MODELS BEING 5152 03:29:29,520 --> 03:29:32,600 USED IN THE TRADITIONAL METHODS 5153 03:29:32,600 --> 03:29:34,920 OF DRUG DEVELOPMENT SHOWS 5154 03:29:34,920 --> 03:29:36,000 SPECIES-SPECIFIC DIFFERENCES. 5155 03:29:36,000 --> 03:29:38,080 WE ALSO ARE LOOKING AT MODELS 5156 03:29:38,080 --> 03:29:39,600 THAT MIMIC STRUCTURE AND 5157 03:29:39,600 --> 03:29:42,880 FUNCTION OF HUMAN DISEASES, OF 5158 03:29:42,880 --> 03:29:43,200 COURSE. 5159 03:29:43,200 --> 03:29:49,000 AND MODELS THAT MEET NEED FOR 5160 03:29:49,000 --> 03:29:49,800 NEW THERAPEUTIC MODALITIES, THAT 5161 03:29:49,800 --> 03:29:51,640 GOES BACK TO THE LAST QUESTION 5162 03:29:51,640 --> 03:29:54,440 BECAUSE MORE AND MORE OF THE 5163 03:29:54,440 --> 03:29:55,680 TREATMENT EVEN FOR SMALL 5164 03:29:55,680 --> 03:29:59,520 MOLECULES ARE BECOMING MORE 5165 03:29:59,520 --> 03:30:03,080 SPECIFIC TO SPECIFIC HUMAN 5166 03:30:03,080 --> 03:30:03,840 MUTATIONS, ANTIBODIES, VACCINES 5167 03:30:03,840 --> 03:30:05,480 ARE MORE HUMAN SPECIFIC IN TERMS 5168 03:30:05,480 --> 03:30:09,160 OF HOW THEY ARE BEING DEVELOPED. 5169 03:30:09,160 --> 03:30:11,000 AND SOMATIC GENE EDITING, LIKE 5170 03:30:11,000 --> 03:30:14,120 COMING INTO VOGUE AND ESPECIALLY 5171 03:30:14,120 --> 03:30:15,600 FOR GENE THERAPIES, ESSENTIALLY 5172 03:30:15,600 --> 03:30:17,000 TESTED ONLY ON HUMAN SEQUENCES 5173 03:30:17,000 --> 03:30:20,000 AND SO YOU EITHER HAVE TO 5174 03:30:20,000 --> 03:30:24,440 HAVE -- TO DEVELOP COST AND TIME 5175 03:30:24,440 --> 03:30:27,600 TO DEVELOP HUMANIZED ANIMAL 5176 03:30:27,600 --> 03:30:31,520 SYSTEM, USING HUMAN TISSUES PUT 5177 03:30:31,520 --> 03:30:35,560 ON MICROPHYSIOLOGICAL SYSTEMS 5178 03:30:35,560 --> 03:30:39,320 WOULD ADDRESS THAT PURPOSE. 5179 03:30:39,320 --> 03:30:42,560 AND SO THE NCATS TISSUE CHIP 5180 03:30:42,560 --> 03:30:44,640 PROGRAM TAKES INTO ACCOUNT 5181 03:30:44,640 --> 03:30:47,920 FACTORS INTO CONSIDERATION, AND 5182 03:30:47,920 --> 03:30:50,560 REALLY IS INTERDISCIPLINARY 5183 03:30:50,560 --> 03:30:51,320 APPROACH BRINGING TOGETHER 5184 03:30:51,320 --> 03:30:52,520 MULTI-DISCIPLINES, OUR TEAM, 5185 03:30:52,520 --> 03:30:56,560 PROJECT TEAMS, ARE TYPICALLY 5186 03:30:56,560 --> 03:30:57,840 MULTI-DISCIPLINARY, MADE OF 5187 03:30:57,840 --> 03:31:00,400 BIOMEDICAL ENGINEERS, STEM CELL 5188 03:31:00,400 --> 03:31:01,640 BIOLOGISTS, MICROFLUIDIC 5189 03:31:01,640 --> 03:31:04,440 EXPERTS, AND PHARMACOLOGISTS AND 5190 03:31:04,440 --> 03:31:04,960 TOXICOLOGISTS. 5191 03:31:04,960 --> 03:31:06,040 ALL INFORMING AND COMING 5192 03:31:06,040 --> 03:31:09,480 TOGETHER TO SEE HOW WE COULD 5193 03:31:09,480 --> 03:31:11,120 DEVELOP SYSTEMS THAT WOULD MIMIC 5194 03:31:11,120 --> 03:31:13,200 AT LEAST TEN MAJOR ORGAN SYSTEMS 5195 03:31:13,200 --> 03:31:20,240 IN THE BODY, ALL LISTED HERE, 5196 03:31:20,240 --> 03:31:21,680 CIRCULATORY, ENDOCRINE, 5197 03:31:21,680 --> 03:31:28,880 GASTRODES SPINDLE -- 5198 03:31:28,880 --> 03:31:30,520 GASTROINTESTINAL, IMMUNE, SKIN. 5199 03:31:30,520 --> 03:31:33,280 THEY ARE MORE TISSUES ON CHIPS, 5200 03:31:33,280 --> 03:31:35,680 BECAUSE WE GO FROM THE BOTTOM 5201 03:31:35,680 --> 03:31:42,360 UP, LOOK AT THE BASIC FUNCTIONAL 5202 03:31:42,360 --> 03:31:48,480 UNIT OF ORGAN SYSTEM, SUCH AS 5203 03:31:48,480 --> 03:31:52,400 LUNGS, WITH ALVEOLI, AIR SACS, 5204 03:31:52,400 --> 03:31:55,920 RENDERING THAT HAS BEEN 5205 03:31:55,920 --> 03:32:03,400 MENTIONED IN THIS WORKSHOP A FEW 5206 03:32:03,400 --> 03:32:06,760 TIMES, EMULI, CYCLIC VACUUMING, 5207 03:32:06,760 --> 03:32:08,760 STRETCHING MEMBRANE, BLUE WOULD 5208 03:32:08,760 --> 03:32:12,160 BE HUMAN LUNG EPITHELIAL CELLS, 5209 03:32:12,160 --> 03:32:12,880 VASCULAR ENDOTHELIUM ON THE 5210 03:32:12,880 --> 03:32:15,240 BOTTOM SIDE OF THE MEMBRANE, AND 5211 03:32:15,240 --> 03:32:16,880 THE LUNG EPITHELIAL CELLS IS 5212 03:32:16,880 --> 03:32:22,120 EXPOSED TO AIR SO THERE'S 5213 03:32:22,120 --> 03:32:23,120 AIR-LIQUID INTERFACE BECAUSE THE 5214 03:32:23,120 --> 03:32:25,960 BOTTOM WOULD BE MEDIA FLOW. 5215 03:32:25,960 --> 03:32:28,560 THAT'S STRETCHING BY ITSELF, 5216 03:32:28,560 --> 03:32:30,840 BIOMECHANICAL PROPERTIES OF THE 5217 03:32:30,840 --> 03:32:33,520 CHIP ALLOWS FOR MORE PHYSIOLOGIC 5218 03:32:33,520 --> 03:32:34,920 RESPONSE OF THE CELLS. 5219 03:32:34,920 --> 03:32:38,000 SO THAT'S THAT EXAMPLE OF THE 5220 03:32:38,000 --> 03:32:41,240 EMULATE SINGLE ORGAN CHIP THAT 5221 03:32:41,240 --> 03:32:45,480 TYLER ADEQUATELY DESCRIBED IN 5222 03:32:45,480 --> 03:32:45,960 HIS PRESENTATION. 5223 03:32:45,960 --> 03:32:48,120 WE ALSO HAVE EFFORTS TO FORM 5224 03:32:48,120 --> 03:32:49,240 MULTI-ORGAN SYSTEMS. 5225 03:32:49,240 --> 03:32:53,440 THIS IS AN EXAMPLE OF A COMPANY 5226 03:32:53,440 --> 03:32:57,240 THAT NCATS FUNDED, IT'S ABOUT 5227 03:32:57,240 --> 03:33:02,800 THE SIZE OF YOUR iPHONE, FIVE 5228 03:33:02,800 --> 03:33:06,760 COMPARTMENTS, CONTAINING LIVER, 5229 03:33:06,760 --> 03:33:08,400 MUSCLE TISSUE, BOTH SKELETAL, 5230 03:33:08,400 --> 03:33:12,680 AND CARDIAC MUSCLES, AS WELL AS 5231 03:33:12,680 --> 03:33:21,240 KIDNEY AND BRAIN CELLS IN THE 5232 03:33:21,240 --> 03:33:22,200 OUTER COMPARTMENTS. 5233 03:33:22,200 --> 03:33:23,840 WE STARTED WORKING ON THIS 5234 03:33:23,840 --> 03:33:25,600 PROGRAM IN 2012 SPECIFICALLY 5235 03:33:25,600 --> 03:33:27,920 FOCUSING ON PRIMARILY HOW TO 5236 03:33:27,920 --> 03:33:28,800 VERY MANY TECHNOLOGY, PRIMARILY 5237 03:33:28,800 --> 03:33:32,160 FIRST LOOKING AT HOW TO PREDICT 5238 03:33:32,160 --> 03:33:32,960 DRUG SAFETY, AND TOXICOLOGY SO 5239 03:33:32,960 --> 03:33:37,200 THESE ARE SOME OF THE FUNDED 5240 03:33:37,200 --> 03:33:39,400 PROJECTS, AND WE WERE JOINED BY 5241 03:33:39,400 --> 03:33:40,840 PARTNERS WITHIN THE NIH, THROUGH 5242 03:33:40,840 --> 03:33:44,560 THE NIH COMMON FUND, NIBIB, NCI, 5243 03:33:44,560 --> 03:33:46,760 NICHD, NIEHS, AND THE OFFICE OF 5244 03:33:46,760 --> 03:33:47,720 RESEARCH FOR WOMEN'S HEALTH. 5245 03:33:47,720 --> 03:33:50,560 JUST TO GIVE AN EXAMPLE OF SOME 5246 03:33:50,560 --> 03:33:52,760 OF THE THINGS THAT ARE BEING 5247 03:33:52,760 --> 03:33:55,080 DONE IN TERMS OF DRUG 5248 03:33:55,080 --> 03:33:56,400 DEVELOPMENT, AND HOW WE'RE 5249 03:33:56,400 --> 03:33:58,720 APPROACHING QUALIFICATION OR IN 5250 03:33:58,720 --> 03:34:00,240 SOME CASES VALIDATION OF THIS 5251 03:34:00,240 --> 03:34:02,520 TECHNOLOGY, THIS IS AN EXAMPLE I 5252 03:34:02,520 --> 03:34:04,080 THINK I'VE HEARD IN THE CONTEXT 5253 03:34:04,080 --> 03:34:06,360 AT LEAST THIS MORNING OF 5254 03:34:06,360 --> 03:34:07,800 SPECIFIC CONTEXT OF USE, SO THIS 5255 03:34:07,800 --> 03:34:12,960 IS A SPECIFIC CONTEXT OF USE FOR 5256 03:34:12,960 --> 03:34:15,360 A LIVER SINUSOID, A LIVER CHIP 5257 03:34:15,360 --> 03:34:18,440 REPRESENTED ESSENTIALLY THE 5258 03:34:18,440 --> 03:34:20,480 LIVER SINUSOID MADE UP OF 5259 03:34:20,480 --> 03:34:24,240 PARENCHYMAL CHANNELS, OF COURSE 5260 03:34:24,240 --> 03:34:27,200 WE HAVE THE HEPATOCYTES, HUMAN 5261 03:34:27,200 --> 03:34:31,120 HEPATOCYTES, ALSO CELLS ARE 5262 03:34:31,120 --> 03:34:36,840 KUPFFER CELLS, ENDOTHELIAL, 5263 03:34:36,840 --> 03:34:44,600 KUPFFER CELLS, VASCULAR 5264 03:34:44,600 --> 03:34:45,960 COMPARTMENT AND PARENCHYMAL 5265 03:34:45,960 --> 03:34:47,000 COMPARTMENT, RESPONSIBLE FOR 5266 03:34:47,000 --> 03:34:49,880 METABOLIZING A NUMBER OF 5267 03:34:49,880 --> 03:34:50,720 MEDICATIONS. 5268 03:34:50,720 --> 03:34:51,720 DRUG INDUCED LIVER INJURY, 5269 03:34:51,720 --> 03:34:53,920 SPECIFIC CONTEXT OF USE THAT 5270 03:34:53,920 --> 03:34:55,560 WE'RE LOOKING AT, IS THE MOST 5271 03:34:55,560 --> 03:34:57,680 COMMON CAUSE OF ACUTE LIVER 5272 03:34:57,680 --> 03:35:00,160 FAILURE, 15 TO 20 PER 100,000, 5273 03:35:00,160 --> 03:35:02,760 AND CERTAINLY ADVERSE DRUG 5274 03:35:02,760 --> 03:35:04,640 REACTIONS IS AN IMPORTANT CAUSE 5275 03:35:04,640 --> 03:35:06,520 OF LIVER INJURY. 5276 03:35:06,520 --> 03:35:11,200 SO IN THIS CASE IF YOU LOOK AT 5277 03:35:11,200 --> 03:35:14,960 EXAMPLE OF DEVELOPMENT OF 5278 03:35:14,960 --> 03:35:17,240 PARTICULAR DRUG, IT WAS 5279 03:35:17,240 --> 03:35:23,040 DEVELOPED AS AN ANTI-VIRAL AGENT 5280 03:35:23,040 --> 03:35:25,440 FOR HEPATITIS B, FIALURIDINE 5281 03:35:25,440 --> 03:35:26,440 WENT THROUGH PRE-CLINICAL 5282 03:35:26,440 --> 03:35:28,960 TESTING IN RATS AND DOGS IN 5283 03:35:28,960 --> 03:35:33,680 VIVO, FDA, GOT APPROVED, KILLED 5284 03:35:33,680 --> 03:35:37,400 FIVE OF THE 15 HUMAN SUBJECTS 5285 03:35:37,400 --> 03:35:40,240 ENROLLED, THIS WAS EARLY PHASE 1 5286 03:35:40,240 --> 03:35:41,440 TRIALS, HEALTHY HUMAN SUBJECTS, 5287 03:35:41,440 --> 03:35:42,720 IT KILLED FIVE. 5288 03:35:42,720 --> 03:35:44,720 FDA WITHDREW IT OF COURSE. 5289 03:35:44,720 --> 03:35:46,000 IN THAT PARTICULAR CASE THE RAT 5290 03:35:46,000 --> 03:35:49,320 AND DOG IN VIVO MODELS DID NOT 5291 03:35:49,320 --> 03:35:54,440 PREDICT TOXICITY. 5292 03:35:54,440 --> 03:35:55,560 SO THE QUESTION BEING ASKED 5293 03:35:55,560 --> 03:35:57,200 WOULD THE HUMAN LIVER CHIP HAVE 5294 03:35:57,200 --> 03:36:07,360 BEEN ABLE TO PREDICTS PREDICT S 5295 03:36:07,360 --> 03:36:08,000 TOXICITY? 5296 03:36:08,000 --> 03:36:12,080 TOOK RAT LIVER CHIP, CONSTRUCTED 5297 03:36:12,080 --> 03:36:16,680 THE SAME WAY AS HUMAN, DOSED 5298 03:36:16,680 --> 03:36:21,040 WITH 0, 1, 20, 30 MICROMOLARS OF 5299 03:36:21,040 --> 03:36:22,560 FIALURIDINE AND STAINED WITH 5300 03:36:22,560 --> 03:36:26,000 RED, TO SHOW FATTY DEPOSITS, AND 5301 03:36:26,000 --> 03:36:27,720 IF THERE'S FATTY DEPOSIT SHOWING 5302 03:36:27,720 --> 03:36:32,200 UP AT YELLOW, AND THAT WOULD BE 5303 03:36:32,200 --> 03:36:35,400 AN INDICATION OF STEATOSIS. 5304 03:36:35,400 --> 03:36:37,040 EVEN WITH INCREASING DOSE OF 5305 03:36:37,040 --> 03:36:40,440 FIALURIDINE THE RAT LIVER CHIP 5306 03:36:40,440 --> 03:36:42,640 DID NOT SHOW STAINING, HUMAN 5307 03:36:42,640 --> 03:36:47,920 LIVER CHIP SHOWED DOSE DEPENDENT 5308 03:36:47,920 --> 03:36:50,360 INCREASE SHOWN HERE BY 5309 03:36:50,360 --> 03:36:51,280 ACCUMULATION OF FATTY DEPOSITS, 5310 03:36:51,280 --> 03:36:56,480 AND THAT CAN BE QUANTITATED ON 5311 03:36:56,480 --> 03:36:57,160 THIS CHART. 5312 03:36:57,160 --> 03:36:59,560 IT'S NOT TO JUST RELY ON 5313 03:36:59,560 --> 03:37:00,360 HISTOLOGICAL MARKERS OR 5314 03:37:00,360 --> 03:37:02,960 MOLECULAR MARKERS BUT ALSO 5315 03:37:02,960 --> 03:37:06,800 LOOKING AT FUNCTION, SO 5316 03:37:06,800 --> 03:37:09,200 FUNCTIONALITY, ALBUMIN SECRETION 5317 03:37:09,200 --> 03:37:10,720 IS ONE OF THE MOST IMPORTANT 5318 03:37:10,720 --> 03:37:12,360 ASSAYS TO LOOK AT LIVER 5319 03:37:12,360 --> 03:37:15,320 FUNCTION, SO IF YOU LOOK AT THE 5320 03:37:15,320 --> 03:37:17,520 RAT LIVER CHIP, VARYING DOSES, 5321 03:37:17,520 --> 03:37:20,920 THERE'S NO CHANGE IN ALBUMIN 5322 03:37:20,920 --> 03:37:24,200 SECRETION, IN THE HUMAN LIVER 5323 03:37:24,200 --> 03:37:25,000 CHIP THERE'S DOUGH DEPENDENT 5324 03:37:25,000 --> 03:37:28,240 DECREASE AND IF YOU LOOK AT 5325 03:37:28,240 --> 03:37:32,560 MOLECULAR MARKERS OF LIVER 5326 03:37:32,560 --> 03:37:37,000 INJURY SUCH AS MIR 122, 5327 03:37:37,000 --> 03:37:39,000 TRANSFERASE, KERATIN, THERE'S 5328 03:37:39,000 --> 03:37:40,760 DOSE DEPENDENT INCREASE IN 5329 03:37:40,760 --> 03:37:45,360 EXPRESSION OF THIS LIVER INJURY 5330 03:37:45,360 --> 03:37:45,840 MARKERS. 5331 03:37:45,840 --> 03:37:48,720 THAT'S ONE DRUG. 5332 03:37:48,720 --> 03:37:53,960 THIS WAS TO SHOW IN TERMS OF 5333 03:37:53,960 --> 03:37:55,280 REPRODUCIBILITY AND ROBUSTNESS 5334 03:37:55,280 --> 03:37:59,720 OF THIS SYSTEM FOR DRUG INDUCED 5335 03:37:59,720 --> 03:38:03,280 LIVER INJURY, 22 COMPOUNDS WITH 5336 03:38:03,280 --> 03:38:06,000 KNOWN HEPATOTOXIC PROPERTIES 5337 03:38:06,000 --> 03:38:07,440 USED, COLLECTIVELY 22 COMPOUNDS 5338 03:38:07,440 --> 03:38:09,520 CAUSED 200 DEATHS JUST LIKE WITH 5339 03:38:09,520 --> 03:38:12,600 THE FIALURIDINE THEY WENT 5340 03:38:12,600 --> 03:38:14,560 THROUGH PRE-CLINICAL STUDY, INTO 5341 03:38:14,560 --> 03:38:16,840 CLINICAL TRIALS, AND KILLED 200 5342 03:38:16,840 --> 03:38:19,480 PATIENTS, ALL 22 COMPOUNDS WERE 5343 03:38:19,480 --> 03:38:20,480 SUBSEQUENTLY WITHDRAWN. 5344 03:38:20,480 --> 03:38:23,080 SO THE QUESTION IS, AGAIN, JUST 5345 03:38:23,080 --> 03:38:24,640 LIKE WITH THE FIALURIDINE, LIVER 5346 03:38:24,640 --> 03:38:26,160 CHIP BEING ABLE TO PREDICT THAT 5347 03:38:26,160 --> 03:38:35,240 AND THE ANSWER IS YES, WITH 87% 5348 03:38:35,240 --> 03:38:36,360 SENSITIVITY, 100% SPECIFICITY 5349 03:38:36,360 --> 03:38:39,080 BEING ABLE TO PREDICT TOXICITY 5350 03:38:39,080 --> 03:38:41,000 THAT ONLY THE SPHEROID MODEL WAS 5351 03:38:41,000 --> 03:38:45,120 ABLE TO SHOW AT BEST 47% 5352 03:38:45,120 --> 03:38:46,040 SENSITIVITY. 5353 03:38:46,040 --> 03:38:50,480 ALL OF THESE ARE NOW PUBLISHED. 5354 03:38:50,480 --> 03:38:53,920 SWITCHING GEARS WE HAVE ALSO IN 5355 03:38:53,920 --> 03:38:56,160 ADDITION TO LOOKING AT SAFETY 5356 03:38:56,160 --> 03:38:58,320 USE OF TISSUE CHIPS, ALSO 5357 03:38:58,320 --> 03:39:01,320 LOOKING AT DISEASE MODELING AND 5358 03:39:01,320 --> 03:39:02,640 EFFICACY STUDIES, IN THIS CASE 5359 03:39:02,640 --> 03:39:04,360 BEING ABLE TO CAPTURE NOT JUST 5360 03:39:04,360 --> 03:39:09,680 NORMAL HUMAN CELLS AND TISSUES 5361 03:39:09,680 --> 03:39:10,600 BUT ALSO LOOKING AT 5362 03:39:10,600 --> 03:39:11,400 PATIENT-DERIVED MATERIALS, IN 5363 03:39:11,400 --> 03:39:15,360 THIS CASE SO WE CAN CAPTURE THE 5364 03:39:15,360 --> 03:39:17,440 DISEASE MECHANISM OR DISEASE 5365 03:39:17,440 --> 03:39:20,480 PATHOLOGY ON THE CHIPS. 5366 03:39:20,480 --> 03:39:23,000 AND OF COURSE TISSUE PHENOTYPE 5367 03:39:23,000 --> 03:39:27,000 OVER WEEKS AND MONTHS, ALSO 5368 03:39:27,000 --> 03:39:28,360 REFLECT MULTI-ORGAN POTENTIAL 5369 03:39:28,360 --> 03:39:29,080 APPROACHESSOLOGY. 5370 03:39:29,080 --> 03:39:32,960 SO THESE ARE FUNDED PROJECTS 5371 03:39:32,960 --> 03:39:35,920 THAT NCATS HAVE DONE. 5372 03:39:35,920 --> 03:39:39,080 MODELING ESSENTIALLY COMMON 5373 03:39:39,080 --> 03:39:40,800 DISEASES LOOKING AT ALZHEIMER'S, 5374 03:39:40,800 --> 03:39:43,360 PARKINSON'S, EVEN TYPE 2 5375 03:39:43,360 --> 03:39:44,400 DIABETES, WITH MULTI-ORGAN 5376 03:39:44,400 --> 03:39:48,240 CHIPS, AS WELL AS RARE DISEASES 5377 03:39:48,240 --> 03:39:52,640 LOOKING AT BART SYNDROME, A RARE 5378 03:39:52,640 --> 03:39:57,120 CARDIOMYOPATHY, ALSO LOOKING AT 5379 03:39:57,120 --> 03:39:59,200 RARE VASCULAR THUNDERSTORMATION, 5380 03:39:59,200 --> 03:40:01,520 NOW BEING STUDIED IN THE CONTEXT 5381 03:40:01,520 --> 03:40:02,720 OF DISEASE MODELING. 5382 03:40:02,720 --> 03:40:05,480 JUST TO GIVE AN EXAMPLE OF THE 5383 03:40:05,480 --> 03:40:11,680 POWER OF THIS TECHNOLOGY BEING 5384 03:40:11,680 --> 03:40:13,360 ABLE TO CAPTURE HUMAN DISEASES 5385 03:40:13,360 --> 03:40:15,560 WHICH TAKES YEARS TO DEVELOP 5386 03:40:15,560 --> 03:40:22,400 ANIMAL MODELS FOR, IN A RARE 5387 03:40:22,400 --> 03:40:24,200 AUTOIMMUNE DISEASE DEMYELINATING 5388 03:40:24,200 --> 03:40:25,600 NEUROPATHY, IN PARTICULAR 5389 03:40:25,600 --> 03:40:31,000 CHRONIC INFLAMMATORY 5390 03:40:31,000 --> 03:40:32,840 DEMYELINATING POLY NEUROPATHY, 5391 03:40:32,840 --> 03:40:33,880 CIDP, MULTI-FOCAL MOTOR 5392 03:40:33,880 --> 03:40:34,200 NEUROPATHY. 5393 03:40:34,200 --> 03:40:35,680 SO THERE ARE NO EXISTING ANIMAL 5394 03:40:35,680 --> 03:40:43,960 MODELS FOR THIS BECAUSE IT'S A 5395 03:40:43,960 --> 03:40:46,600 RARE DISEASE. 5396 03:40:46,600 --> 03:40:52,840 THE ANTIBODIES GENERATED BY THE 5397 03:40:52,840 --> 03:40:55,880 PATIENT ATTACKS THE NERVOUS 5398 03:40:55,880 --> 03:40:58,000 SYSTEM, IN THIS CASE 5399 03:40:58,000 --> 03:40:59,280 NEUROMUSCULAR JUNCTION ON A CHIP 5400 03:40:59,280 --> 03:41:02,560 WAS DEVELOPED CONSISTING OF 5401 03:41:02,560 --> 03:41:05,000 HUMAN PRIMARY SCHWANN CELLS AND 5402 03:41:05,000 --> 03:41:08,040 INDUCE THE PLURIPOTENT CELLS 5403 03:41:08,040 --> 03:41:09,880 DERIVED FROM MOTOR NEURONS, 5404 03:41:09,880 --> 03:41:15,080 AUTOIMMUNE, SO SERA FROM 5405 03:41:15,080 --> 03:41:18,800 PATIENTS ARE COLLECTED, AND THIS 5406 03:41:18,800 --> 03:41:20,360 NEUROMUSCULAR JUNCTION TREATED 5407 03:41:20,360 --> 03:41:21,640 WITH PATIENT SERA, IF THERE IS 5408 03:41:21,640 --> 03:41:27,040 AN IMMUNE RESPONSE YOU CAN SEE 5409 03:41:27,040 --> 03:41:29,520 THIS IN VARIOUS STAINING, GREEN 5410 03:41:29,520 --> 03:41:32,600 FOR SHOWING ACTIVATION OF 5411 03:41:32,600 --> 03:41:35,840 COMPLEMENT PATHWAY C3B AND RED 5412 03:41:35,840 --> 03:41:36,640 SHOWING ACTIVATION AND YELLOW 5413 03:41:36,640 --> 03:41:43,040 WOULD BE LIKE A CO-LOCALIZATION. 5414 03:41:43,040 --> 03:41:44,360 IN THIS EXAMPLE THESE ARE 15 5415 03:41:44,360 --> 03:41:46,720 NEUROMUSCULAR JUNCTIONS ON A 5416 03:41:46,720 --> 03:41:48,440 CHIP, EACH TREATED WITH SERA 5417 03:41:48,440 --> 03:41:50,560 FROM 15 PATIENTS AND AGAIN 5418 03:41:50,560 --> 03:41:55,920 CONSISTENTLY ALL 15 SERA SHOWED 5419 03:41:55,920 --> 03:41:59,040 STAINING, THIS IS AN EXAMPLE OF 5420 03:41:59,040 --> 03:42:04,120 DRUG REPURPOSING, THERE'S AN 5421 03:42:04,120 --> 03:42:06,320 FDA-APPROVED DRUG, TNT 005, 5422 03:42:06,320 --> 03:42:10,600 MONOCLONAL ANTIBODY THAT 5423 03:42:10,600 --> 03:42:12,240 INHIBITS C1S PROTEASE. 5424 03:42:12,240 --> 03:42:14,040 IF YOU PRE-TREAT THE 5425 03:42:14,040 --> 03:42:15,840 NEUROMUSCULAR JUNCTION ON CHIP 5426 03:42:15,840 --> 03:42:18,920 AND ADD THE SERUM, THIS IS WHAT 5427 03:42:18,920 --> 03:42:22,640 YOU GET. 5428 03:42:22,640 --> 03:42:25,160 NO ACTIVATION OF COMPLEMENT, IN 5429 03:42:25,160 --> 03:42:28,760 ANY OF THE -- AGAINST ANY 15 5430 03:42:28,760 --> 03:42:30,760 SERA, SO THIS WAS DEVELOPED 5431 03:42:30,760 --> 03:42:32,720 WITHIN MONTHS AND THE CANDIDATE 5432 03:42:32,720 --> 03:42:34,680 DRUG WAS IDENTIFIED WITHIN 5433 03:42:34,680 --> 03:42:40,600 MONTHS, AND IT'S NOW IN PHASE 2 5434 03:42:40,600 --> 03:42:42,080 CLINICAL TRIALS SPONSORED BY 5435 03:42:42,080 --> 03:42:42,440 SANOFI. 5436 03:42:42,440 --> 03:42:45,080 ONE OF THE THINGS THAT WE HAVE 5437 03:42:45,080 --> 03:42:47,600 BEEN FORTUNATE TO DO AS WELL IS 5438 03:42:47,600 --> 03:42:49,880 TO BE ABLE TO PIVOT TISSUE CHIP 5439 03:42:49,880 --> 03:42:52,760 TECHNOLOGY TO RESPOND TO 5440 03:42:52,760 --> 03:42:53,360 NATIONAL HEALTH EMERGENCIES, 5441 03:42:53,360 --> 03:42:55,960 PRIOR TO THE PANDEMIC WE HAD THE 5442 03:42:55,960 --> 03:42:58,320 OPIOID CRISIS SO WE WERE FUNDED 5443 03:42:58,320 --> 03:43:01,600 TO DEVELOP MODEL SYSTEMS TO 5444 03:43:01,600 --> 03:43:05,120 DEVELOP MODELS THAT COULD MIMIC 5445 03:43:05,120 --> 03:43:07,000 SENSORY PAIN CIRCUITRY, AS YOU 5446 03:43:07,000 --> 03:43:10,920 KNOW MOST MODELS IN PAIN INVOLVE 5447 03:43:10,920 --> 03:43:13,240 RAT AND INVOLVES PUTTING THE 5448 03:43:13,240 --> 03:43:16,040 PAWS ON A HEAT PAD. 5449 03:43:16,040 --> 03:43:18,480 EVEN WITH THAT IT'S STILL 5450 03:43:18,480 --> 03:43:19,320 INADEQUATE. 5451 03:43:19,320 --> 03:43:22,800 WE'VE BEEN DEVELOPING MODELS TO 5452 03:43:22,800 --> 03:43:24,080 ALSO MIMIC THE BLOOD-BRAIN 5453 03:43:24,080 --> 03:43:25,920 BARRIER, AND WITH THE PANDEMIC 5454 03:43:25,920 --> 03:43:29,960 BEING ABLE TO ALSO AS NICOLE 5455 03:43:29,960 --> 03:43:34,360 INDICATED IN HER TALK NOT VERY 5456 03:43:34,360 --> 03:43:36,760 MANY ANIMALS, THE FERRET AND 5457 03:43:36,760 --> 03:43:38,400 HAMSTER SUBJECT TO INFECTION BY 5458 03:43:38,400 --> 03:43:42,640 SARS-COV-2, SO WE WERE ABLE TO 5459 03:43:42,640 --> 03:43:44,520 SHOW THAT TISSUE CHIPS CAN BE 5460 03:43:44,520 --> 03:43:46,040 DEVELOPED TO BE ABLE TO 5461 03:43:46,040 --> 03:43:48,240 UNDERSTAND MODEL INFECTION AND 5462 03:43:48,240 --> 03:43:51,960 ALSO TO TEST CANDIDATE DRUGS AS 5463 03:43:51,960 --> 03:43:52,720 WELL AS VACCINES. 5464 03:43:52,720 --> 03:43:55,920 ONE OF THE THINGS THAT WE HAVE 5465 03:43:55,920 --> 03:43:59,880 BEEN FORTUNATE TO HAVE IS A 5466 03:43:59,880 --> 03:44:00,880 PARTNERSHIP WITHIN NCATS, NASA, 5467 03:44:00,880 --> 03:44:03,160 CENTER FOR ADVANCEMENT OF 5468 03:44:03,160 --> 03:44:05,480 SCIENCE IN SPACE, INTERNATIONAL 5469 03:44:05,480 --> 03:44:05,960 SPACE STATION, NATIONAL 5470 03:44:05,960 --> 03:44:07,440 LABORATORY, THIS IS ALSO AN 5471 03:44:07,440 --> 03:44:09,160 EXAMPLE WHERE WE'RE PUSHING THE 5472 03:44:09,160 --> 03:44:11,800 BOUNDARIES IN THIS CASE INTO 5473 03:44:11,800 --> 03:44:16,560 OUTER SPACE TO MODEL DISEASES, 5474 03:44:16,560 --> 03:44:19,040 TYPICALLY WILL TAKE YEARS IF NOT 5475 03:44:19,040 --> 03:44:20,880 DECADES TO MODEL HERE ON EARTH, 5476 03:44:20,880 --> 03:44:24,600 BUT AS IT TURNED OUT UNDER 5477 03:44:24,600 --> 03:44:26,800 EXPOSURE OF THE MICRO GRAVITY 5478 03:44:26,800 --> 03:44:28,520 ENVIRONMENT ACCELERATING AGING 5479 03:44:28,520 --> 03:44:30,480 CAN BE MIMICKED WITHIN WEEKS, 5480 03:44:30,480 --> 03:44:32,280 EXPOSURE TO MICRO GRAVITY, SO WE 5481 03:44:32,280 --> 03:44:34,720 HAVE PROJECTS THAT HAVE GONE TO 5482 03:44:34,720 --> 03:44:45,240 THE SPACE STATION, THE CULTURE 5483 03:45:14,760 --> 03:45:16,120 LIFE OF ORGANS AND CHIPS. 5484 03:45:16,120 --> 03:45:19,160 WHAT THEY HAVE BEEN DEVELOPED TO 5485 03:45:19,160 --> 03:45:21,880 ADDRESS THE FDA REQUIREMENT OF 5486 03:45:21,880 --> 03:45:23,640 28-DAY EXPOSURE, AND SO MOST OF 5487 03:45:23,640 --> 03:45:24,760 THE CHIPS HAVE CERTAINLY MET 5488 03:45:24,760 --> 03:45:28,440 THAT AND THEY ARE GOING ON FOR 5489 03:45:28,440 --> 03:45:30,880 30 DAYS UP TO IN SOME CASES 5490 03:45:30,880 --> 03:45:32,840 THREE MONTHS, BUT WE WANTED TO 5491 03:45:32,840 --> 03:45:41,720 SEE IF WE CAN PUSH THIS SYSTEM 5492 03:45:41,720 --> 03:45:47,080 AND DEVELOP PLATFORMS TO EXTEND 5493 03:45:47,080 --> 03:45:50,280 TO SIX MONTHS LOOKING AT DISEASE 5494 03:45:50,280 --> 03:45:51,240 MECHANISMS, LOOKING AT BEING 5495 03:45:51,240 --> 03:45:54,760 ABLE TO HAVE A SYSTEM IN A WOULD 5496 03:45:54,760 --> 03:45:56,800 SUBJECT -- THAT WOULD BE SUBJECT 5497 03:45:56,800 --> 03:45:59,040 TO CHRONIC EXPOSURE IN DRUGS AND 5498 03:45:59,040 --> 03:46:01,280 THINGS INTERESTING TO THIS GROUP 5499 03:46:01,280 --> 03:46:08,440 FOR ENVIRONMENTAL AGENTS AS 5500 03:46:08,440 --> 03:46:08,640 WELL. 5501 03:46:08,640 --> 03:46:10,640 ANOTHER AREA, THE MORE RECENT 5502 03:46:10,640 --> 03:46:15,000 ONE, CLINICAL TRIALS ON CHIPS. 5503 03:46:15,000 --> 03:46:17,400 CO-FUNDED BY NCI, NICHD, AND 5504 03:46:17,400 --> 03:46:21,920 NIAMS, AND THE QUESTION HERE IS 5505 03:46:21,920 --> 03:46:24,440 CAN WE DEVELOP TISSUE CHIPS THAT 5506 03:46:24,440 --> 03:46:25,400 CAN INCORPORATE DIVERSITY, NOT 5507 03:46:25,400 --> 03:46:27,080 ONLY IN TERMS OF PATIENT 5508 03:46:27,080 --> 03:46:32,080 DIVERSITY, IN TERMS OF PATIENT 5509 03:46:32,080 --> 03:46:34,520 POPULATION, BUT ALSO PEDIATRIC 5510 03:46:34,520 --> 03:46:36,440 POPULATIONS, VARIOUS GROUPS THAT 5511 03:46:36,440 --> 03:46:42,040 ARE AMENABLE OR NOT AMENABLE BUT 5512 03:46:42,040 --> 03:46:45,880 SUSCEPTIBLE IN TERMS OF 5513 03:46:45,880 --> 03:46:46,840 ETHNIC-SPECIFIC OR 5514 03:46:46,840 --> 03:46:47,600 POPULATION-SPECIFIC GROUPS THAT 5515 03:46:47,600 --> 03:46:50,680 MIGHT BE AT RISK TO CERTAIN 5516 03:46:50,680 --> 03:46:51,160 DISEASES. 5517 03:46:51,160 --> 03:46:53,520 AND BE ABLE TO THEN INFORM HOW 5518 03:46:53,520 --> 03:46:55,160 TO INFORM CLINICAL TRIALS IN 5519 03:46:55,160 --> 03:46:57,080 TERMS OF RECRUITMENT, ABLE TO 5520 03:46:57,080 --> 03:47:00,000 STRATIFY THE PATIENT, VERY MANY 5521 03:47:00,000 --> 03:47:00,800 CLINICALLY RELEVANT BIOMARKERS 5522 03:47:00,800 --> 03:47:02,920 WITH THE GOAL OF ESSENTIALLY 5523 03:47:02,920 --> 03:47:05,360 SHORTENING THE CLINICAL TRIAL 5524 03:47:05,360 --> 03:47:06,800 PIPELINE, AND MAKING IT MORE 5525 03:47:06,800 --> 03:47:09,720 SUCCESSFUL BY IDENTIFYING 5526 03:47:09,720 --> 03:47:11,160 PATIENTS WHO ARE MOST LIKELY TO 5527 03:47:11,160 --> 03:47:13,000 BE SUBJECT TO ADVERSE EVENT AND 5528 03:47:13,000 --> 03:47:16,680 THOSE MOST LIKELY TO RESPOND TO 5529 03:47:16,680 --> 03:47:17,280 THE TREATMENT. 5530 03:47:17,280 --> 03:47:21,000 AND SO THESE ARE ESSENTIALLY 5531 03:47:21,000 --> 03:47:24,760 LOOKING AT INCORPORATING UPWARDS 5532 03:47:24,760 --> 03:47:28,360 OF 200 PATIENTS ON 200 CHIPS, SO 5533 03:47:28,360 --> 03:47:31,320 MANY INDIVIDUALS BEING 5534 03:47:31,320 --> 03:47:32,520 REPRESENTED ON THE CHIPS, 5535 03:47:32,520 --> 03:47:34,160 REPRESENTING AGAIN THE PATIENT 5536 03:47:34,160 --> 03:47:36,360 DIVERSITY AS WELL, AS WELL AS 5537 03:47:36,360 --> 03:47:38,240 POPULATION DIVERSITY, AND THEN 5538 03:47:38,240 --> 03:47:40,200 ACTUALLY RUN IT ALONGSIDE AN 5539 03:47:40,200 --> 03:47:42,480 ONGOING CLINICAL TRIAL SO THIS 5540 03:47:42,480 --> 03:47:45,520 INVOLVES PARTNERSHIP WITH 5541 03:47:45,520 --> 03:47:46,280 PHARMA, AND TESTING ALONGSIDE 5542 03:47:46,280 --> 03:47:49,040 THE CLINICAL TRIALS TO SEE IF 5543 03:47:49,040 --> 03:47:51,240 THERE'S GOING TO BE CORRELATION 5544 03:47:51,240 --> 03:47:54,320 OF THE RESULTS FROM THE PATIENT 5545 03:47:54,320 --> 03:47:55,520 TRIALS VERSUS THOSE RESULTS 5546 03:47:55,520 --> 03:47:58,120 COMING OUT FROM THE CHIPS. 5547 03:47:58,120 --> 03:48:02,280 SO THESE ARE SOME OF THE 5548 03:48:02,280 --> 03:48:06,840 PROJECTS THAT WE'RE FUNDING FROM 5549 03:48:06,840 --> 03:48:13,000 NON-ALCOHOL FATTY DELIVER 5550 03:48:13,000 --> 03:48:15,920 DISEASE, PROGERIA, MUSCULAR 5551 03:48:15,920 --> 03:48:19,040 DYSTROPHY, TEND INFLAMMATION, 5552 03:48:19,040 --> 03:48:20,760 ALS, HEART DISEASE, PRE-TERM 5553 03:48:20,760 --> 03:48:23,600 BIRTH, PLACENTA ON A CHIP, AND 5554 03:48:23,600 --> 03:48:25,800 THEN PROSTATE CANCER, METASTASIS 5555 03:48:25,800 --> 03:48:29,640 INTO THE BONE MARROW. 5556 03:48:29,640 --> 03:48:31,360 SWITCHING GEARS WE'RE ALSO OF 5557 03:48:31,360 --> 03:48:34,440 COURSE INTERESTED IN DEVELOPING 5558 03:48:34,440 --> 03:48:35,400 TECHNOLOGY AND BUILDING 5559 03:48:35,400 --> 03:48:36,960 CONFIDENCE, INTO TECHNOLOGY SO 5560 03:48:36,960 --> 03:48:40,840 IT COULD LEAD TO WIDESPREAD USE 5561 03:48:40,840 --> 03:48:43,400 AND COMMERCIALIZATION, SO THIS 5562 03:48:43,400 --> 03:48:45,160 IS ESSENTIALLY A THREE-STEP 5563 03:48:45,160 --> 03:48:47,040 VALIDATION PROCESS THAT WE PUT 5564 03:48:47,040 --> 03:48:51,120 TOGETHER AS PART OF OUR 5565 03:48:51,120 --> 03:48:51,680 FRAMEWORK, PHYSIOLOGICAL 5566 03:48:51,680 --> 03:48:54,680 VALIDATION WOULD BE AS MENTIONED 5567 03:48:54,680 --> 03:48:55,640 IN PREVIOUS SLIDES TO MIMIC 5568 03:48:55,640 --> 03:48:58,320 ORGAN FUNCTION AT THE BASICS 5569 03:48:58,320 --> 03:49:00,120 FUNCTIONAL UNIT, AND USE THEM TO 5570 03:49:00,120 --> 03:49:03,200 SEE THE RESPONSE ON THE SET OF 5571 03:49:03,200 --> 03:49:05,160 REFERENCE COMPOUND OR TRAINING 5572 03:49:05,160 --> 03:49:08,320 COMPOUNDS, I'VE SHOWN WITH THE 5573 03:49:08,320 --> 03:49:08,960 FIALURIDINE AS AN EXAMPLE. 5574 03:49:08,960 --> 03:49:10,720 ALL OF THOSE HAVE BEEN 5575 03:49:10,720 --> 03:49:13,000 PUBLISHED, AS A RESULTS HAVE 5576 03:49:13,000 --> 03:49:14,800 BEEN PUBLISHED. 5577 03:49:14,800 --> 03:49:17,840 NEXT WE SET UP ANALYTICAL 5578 03:49:17,840 --> 03:49:20,080 VALIDATION, ESSENTIALLY CREATING 5579 03:49:20,080 --> 03:49:21,520 OR ESTABLISHING INDEPENDENT 5580 03:49:21,520 --> 03:49:24,680 TESTING CENTERS, THAT WOULD TEST 5581 03:49:24,680 --> 03:49:25,320 ROBUSTNESS, REPRODUCIBILITY, 5582 03:49:25,320 --> 03:49:27,280 RELIABILITY, RELEVANCE AS WELL 5583 03:49:27,280 --> 03:49:29,840 AS PORTABILITY OF THIS 5584 03:49:29,840 --> 03:49:30,480 TECHNOLOGY, THESE TECHNOLOGIES, 5585 03:49:30,480 --> 03:49:32,120 BY PUTTING THEM INTO TESTING 5586 03:49:32,120 --> 03:49:36,160 CENTERS THAT HAVE NOT WORKED ON 5587 03:49:36,160 --> 03:49:37,480 THIS TISSUE CHIP SYSTEMS, BUT 5588 03:49:37,480 --> 03:49:38,560 BEING ABLE TO SHOW THAT THEY CAN 5589 03:49:38,560 --> 03:49:40,560 IN THEIR OWN HANDS BE ABLE TO 5590 03:49:40,560 --> 03:49:42,720 REPLICATE THE DATA THAT WAS 5591 03:49:42,720 --> 03:49:43,280 GENERATED BY THE DEVELOPERS. 5592 03:49:43,280 --> 03:49:47,320 AND SO IN THAT REGARD WE HAVE 5593 03:49:47,320 --> 03:49:53,360 FUNDED -- M.I.T. IS A TESTING 5594 03:49:53,360 --> 03:49:55,440 CENTER, TEXAS A & M, AND 5595 03:49:55,440 --> 03:49:56,960 CREATING DATABASE AT UNIVERSITY 5596 03:49:56,960 --> 03:49:57,600 OF PITTSBURGH. 5597 03:49:57,600 --> 03:50:01,240 THE LAST STEP IN THE VALIDATION 5598 03:50:01,240 --> 03:50:02,000 FRAMEWORK IS INDUSTRIAL 5599 03:50:02,000 --> 03:50:03,640 VALIDATION, WHERE INDUSTRY AND 5600 03:50:03,640 --> 03:50:04,400 REGULATORY AGENCIES ARE NOW 5601 03:50:04,400 --> 03:50:07,280 STARTING TO USE THIS HEAVILY, I 5602 03:50:07,280 --> 03:50:09,520 WON'T GO INTO THAT IN MY TALK 5603 03:50:09,520 --> 03:50:12,280 BUT THERE'S PLENTY OF PAPERS TO 5604 03:50:12,280 --> 03:50:13,960 SHOW THERE'S INDUSTRY USE, AS 5605 03:50:13,960 --> 03:50:17,440 WELL AS FDA INTEREST OR 5606 03:50:17,440 --> 03:50:18,960 REGULATORY INTEREST, AND THIS IS 5607 03:50:18,960 --> 03:50:21,040 DONE EITHER IN THEIR OWN 5608 03:50:21,040 --> 03:50:24,000 LABORATORIES OR THROUGH A 5609 03:50:24,000 --> 03:50:24,440 CRO-TYPE ENVIRONMENT. 5610 03:50:24,440 --> 03:50:28,240 IN THAT REGARD OUR TESTING 5611 03:50:28,240 --> 03:50:31,520 CENTERS EVOLVE INTO LIKE M.I.T. 5612 03:50:31,520 --> 03:50:33,040 BECAME JAVELIN BIOTECH, NOW A 5613 03:50:33,040 --> 03:50:35,920 CRO, AND TEXAS A & M IS NOW A 5614 03:50:35,920 --> 03:50:39,400 TESTING CONSORTIUM WHICH IS A 5615 03:50:39,400 --> 03:50:45,040 PAY FOR PLAY MODEL, MPS DATABASE 5616 03:50:45,040 --> 03:50:46,960 NOW ALSO SELF-STAINING IN THE 5617 03:50:46,960 --> 03:50:49,560 SENSE THEY HAVE BOTH DATA THAT'S 5618 03:50:49,560 --> 03:50:54,080 FREELY ACCESSIBLE TO THE PUBLIC 5619 03:50:54,080 --> 03:50:55,080 AND FIRE WALL-PROTECTED DATA 5620 03:50:55,080 --> 03:51:01,440 SITE THINGS AND CALLED A 5621 03:51:01,440 --> 03:51:02,720 BIOCYSTIC ANALYTICS PLATFORM, 5622 03:51:02,720 --> 03:51:04,920 ESSENTIALLY TAKES IN DATA FROM 5623 03:51:04,920 --> 03:51:07,320 TISSUE CHIPS AND INCORPORATION 5624 03:51:07,320 --> 03:51:10,680 THAT WITH CLINICAL DATA, 5625 03:51:10,680 --> 03:51:12,040 PRE-CLINICAL DATA, ALL THE 5626 03:51:12,040 --> 03:51:13,760 UNIVERSE OF COMPOUNDS AND 5627 03:51:13,760 --> 03:51:14,880 CHEMISTRIES HAVE BEEN TESTED IN 5628 03:51:14,880 --> 03:51:20,440 HUMANS TO BE ABLE TO INFORM 5629 03:51:20,440 --> 03:51:21,080 MODEL REPRODUCIBILITY, IDENTIFY 5630 03:51:21,080 --> 03:51:26,160 COMPOUNDS THAT ARE SAFE AND 5631 03:51:26,160 --> 03:51:26,800 EFFECTIVEE DISEASE PROGRESSION, 5632 03:51:26,800 --> 03:51:34,280 AS WELL AS DEVELOP MODELS FOR 5633 03:51:34,280 --> 03:51:35,600 ADME AND TOXICITY STUDIES. 5634 03:51:35,600 --> 03:51:38,320 TYLER MENTIONED SOME OF THIS IN 5635 03:51:38,320 --> 03:51:48,040 HIS PRESENTATION SO THERE'S 5636 03:51:48,040 --> 03:51:50,040 TISS-USE, EMULATE, BIO, SPINOFF 5637 03:51:50,040 --> 03:51:55,280 COMPANIES OR STARTUPS, WORKING 5638 03:51:55,280 --> 03:51:59,360 ON VARIOUS ASPECTS OF MIMICKING 5639 03:51:59,360 --> 03:52:00,840 HUMAN PHYSIOLOGY AN FUNCTION AND 5640 03:52:00,840 --> 03:52:04,400 TO A CERTAIN DEGREE NIH HAS 5641 03:52:04,400 --> 03:52:05,240 SUPPORTED THESE COMPANIES 5642 03:52:05,240 --> 03:52:06,880 THROUGH SMALL BUSINESS EFFORTS, 5643 03:52:06,880 --> 03:52:08,080 WHICH IS ALSO SIGNIFICANT IN THE 5644 03:52:08,080 --> 03:52:10,640 SENSE THAT WE ARE EXPECTING 5645 03:52:10,640 --> 03:52:14,960 REALLY A BIG JUMP IN THE USE OF 5646 03:52:14,960 --> 03:52:17,520 THIS TECHNOLOGY, FOR EXAMPLE, IN 5647 03:52:17,520 --> 03:52:20,600 STUDY DONE SHOWING THE CURRENT 5648 03:52:20,600 --> 03:52:23,040 UTILITY OF TISSUE CHIPS, IT'S 5649 03:52:23,040 --> 03:52:24,440 GOING TO GROW TO A $600 MEDICAL 5650 03:52:24,440 --> 03:52:28,000 ENTERPRISE IN A FEW YEARS FROM 5651 03:52:28,000 --> 03:52:32,200 NOW, IN 2028, WITH ABOUT A 40% 5652 03:52:32,200 --> 03:52:36,240 ANNUAL GROWTH RATE. 5653 03:52:36,240 --> 03:52:38,760 JUST TO SUMMARIZE, ASPECTS WERE 5654 03:52:38,760 --> 03:52:40,600 TISSUE CHIPS EMPLOYED, GOES FROM 5655 03:52:40,600 --> 03:52:43,360 EARLIEST STAGES OF DRUG 5656 03:52:43,360 --> 03:52:44,880 DEVELOPMENT FROM TARGET 5657 03:52:44,880 --> 03:52:47,720 IDENTIFICATION AND VALIDATION TO 5658 03:52:47,720 --> 03:52:48,400 CLINICAL ASSESSMENT, AND 5659 03:52:48,400 --> 03:52:51,080 CERTAINLY IT'S ALSO GOING TO BE, 5660 03:52:51,080 --> 03:52:55,520 YOU KNOW, ANTICIPATED TO BE A 5661 03:52:55,520 --> 03:52:58,440 HUGE COST SAVINGS. 5662 03:52:58,440 --> 03:53:04,000 I THINK WE FROZE. 5663 03:53:04,000 --> 03:53:04,360 YEP. 5664 03:53:04,360 --> 03:53:07,000 SO, WITH ANTICIPATED UP TO 26% 5665 03:53:07,000 --> 03:53:09,760 COST SAVINGS IN DRUG DEVELOPMENT 5666 03:53:09,760 --> 03:53:11,280 COST, IN FIVE YEARS, EVEN AT 5667 03:53:11,280 --> 03:53:13,240 JUST CURRENT RATE OF USAGE BUT 5668 03:53:13,240 --> 03:53:14,440 OF COURSE WE'RE SEEING AN 5669 03:53:14,440 --> 03:53:17,880 INCREASE IN USE OF THIS 5670 03:53:17,880 --> 03:53:18,160 TECHNOLOGY. 5671 03:53:18,160 --> 03:53:25,840 LASTLY I'D LIKE TO PUT IN A PLUG 5672 03:53:25,840 --> 03:53:28,240 FOR MICROPHYSIOLOGICAL WORLD 5673 03:53:28,240 --> 03:53:30,120 SUMMIT, SOMETHING NCATS 5674 03:53:30,120 --> 03:53:32,960 ESTABLISHED BY FUNDING 5675 03:53:32,960 --> 03:53:33,520 CONFERENCE GRANT TO HOPKINS, 5676 03:53:33,520 --> 03:53:34,480 JOHNS HOPKINS UNIVERSITY, AND 5677 03:53:34,480 --> 03:53:37,440 OUR GOAL IS TO REALLY BRING THE 5678 03:53:37,440 --> 03:53:39,080 INTERNATIONAL COMMUNITY THAT'S 5679 03:53:39,080 --> 03:53:41,600 WORKING ON TISSUE CHIPS SO WE 5680 03:53:41,600 --> 03:53:43,120 CAN WORK TOWARDS GLOBAL 5681 03:53:43,120 --> 03:53:45,560 HARMONIZATION OF REGULATORY USE 5682 03:53:45,560 --> 03:53:47,760 AND STANDARDIZATION OF 5683 03:53:47,760 --> 03:53:50,160 PLATFORMS, AS WELL AS TO TRAIN 5684 03:53:50,160 --> 03:53:52,120 THE NEXT GENERATION OF 5685 03:53:52,120 --> 03:53:54,080 SCIENTISTS OF ESTABLISHING 5686 03:53:54,080 --> 03:53:54,880 INTERNATIONAL MICROPHYSIOLOGICAL 5687 03:53:54,880 --> 03:53:57,320 SYSTEMS SOCIETY THAT ACTUALLY 5688 03:53:57,320 --> 03:53:59,040 WOULD BE FORMALLY ANNOUNCED AT 5689 03:53:59,040 --> 03:54:01,320 THE BERLIN CONFERENCE NEXT 5690 03:54:01,320 --> 03:54:02,920 MONTH, INAUGURAL CONFERENCE WAS 5691 03:54:02,920 --> 03:54:04,960 LAST YEAR IN NEW ORLEANS, AND 5692 03:54:04,960 --> 03:54:08,120 WE'RE HOPING TO RETURN BACK TO 5693 03:54:08,120 --> 03:54:10,520 THE UNITED STATES IN 2024. 5694 03:54:10,520 --> 03:54:11,800 WITH THAT, I'LL JUST END. 5695 03:54:11,800 --> 03:54:13,440 THIS IS MY SUMMARY SLIDE IN 5696 03:54:13,440 --> 03:54:15,400 TERMS OF THE TISSUE PROGRAM, 5697 03:54:15,400 --> 03:54:18,720 WORKING WITH THE DEVELOPERS AND 5698 03:54:18,720 --> 03:54:20,560 SUPPLIERS, WITH PHARMA 5699 03:54:20,560 --> 03:54:23,960 COMPANIES, REGULATORY AGENCIES, 5700 03:54:23,960 --> 03:54:26,000 IDENTIFYING COMMON AREAS, AND 5701 03:54:26,000 --> 03:54:27,360 CONSORTIUM OF INVESTIGATORS CAN 5702 03:54:27,360 --> 03:54:31,600 WORK WITH PHARMA AND REGULATORY 5703 03:54:31,600 --> 03:54:32,840 AGENCIES, IN BUILDING TOGETHER 5704 03:54:32,840 --> 03:54:35,320 PLATFORMS THAT CAN BE ENABLING 5705 03:54:35,320 --> 03:54:37,640 AND WOULD CERTAINLY STREAMLINE 5706 03:54:37,640 --> 03:54:40,160 COST AND EFFICIENCY OF DRUG 5707 03:54:40,160 --> 03:54:42,000 DEVELOPMENT AND I'VE SHOWN 5708 03:54:42,000 --> 03:54:43,560 HOPEFULLY BRIEFLY IN MY 5709 03:54:43,560 --> 03:54:44,640 PRESENTATION DEMONSTRATION IN 5710 03:54:44,640 --> 03:54:46,920 TERMS OF TOXIN SAFETY STUDIES, 5711 03:54:46,920 --> 03:54:50,000 HOW WE ESTABLISH TESTING CENTERS 5712 03:54:50,000 --> 03:54:50,880 AND DATABASE CENTERS, 5713 03:54:50,880 --> 03:54:52,080 DEMONSTRATION AND VALIDATION FOR 5714 03:54:52,080 --> 03:54:55,680 RARE AND COMMON DISEASE 5715 03:54:55,680 --> 03:54:57,160 MODELING, CLINICAL TRIALS ON 5716 03:54:57,160 --> 03:55:00,760 CHIPS, ADOPTION AND USE BY 5717 03:55:00,760 --> 03:55:06,000 PHARMA AND DRUG DEVELOPMENT, 5718 03:55:06,000 --> 03:55:08,960 HARMONIZATION, TRAINING OF NEXT 5719 03:55:08,960 --> 03:55:10,800 GENERATION SCIENTISTS, OUR BIG 5720 03:55:10,800 --> 03:55:12,920 NEXT STEP WITHIN NCATS IS 5721 03:55:12,920 --> 03:55:14,120 ESTABLISHMENT, I HAVEN'T PUT A 5722 03:55:14,120 --> 03:55:16,520 CHECK MARK THERE, BUT LATER THIS 5723 03:55:16,520 --> 03:55:18,000 YEAR WE'LL BE ANNOUNCING 5724 03:55:18,000 --> 03:55:20,360 ESTABLISHMENT OF TRANSLATIONAL 5725 03:55:20,360 --> 03:55:24,200 CENTERS FOR MPS WHICH WOULD BE 5726 03:55:24,200 --> 03:55:27,040 U.S.-BASED CENTERS THAT WOULD 5727 03:55:27,040 --> 03:55:30,520 SEEK TO QUALIFY MANY OF THE 5728 03:55:30,520 --> 03:55:31,120 PLATFORMS AS DRUG DEVELOPMENT 5729 03:55:31,120 --> 03:55:36,520 TOOLS SO THAT THE FDA CAN 5730 03:55:36,520 --> 03:55:38,520 ACTUALLY FORMALLY RECOGNIZE THEM 5731 03:55:38,520 --> 03:55:43,040 AS TOOLS AND SO THEN BE ABLE TO 5732 03:55:43,040 --> 03:55:44,120 LEAD TO COMMERCIALIZATION AND 5733 03:55:44,120 --> 03:55:49,480 SCALE OF PRODUCTION. 5734 03:55:49,480 --> 03:55:51,000 AND MY ACKNOWLEDGMENT SLIDE, 5735 03:55:51,000 --> 03:55:53,640 PRIVILEGED WORKING WITH A VERY 5736 03:55:53,640 --> 03:55:55,960 TALENTED GROUP OF PEOPLE WITHIN 5737 03:55:55,960 --> 03:55:57,160 MY OFFICE, THE REST OF THE NIH 5738 03:55:57,160 --> 03:56:00,000 AND SOME OF THE PARTNERS WE HAVE 5739 03:56:00,000 --> 03:56:00,760 ACROSS THE VARIOUS AGENCIES. 5740 03:56:00,760 --> 03:56:02,200 THANK YOU VERY MUCH. 5741 03:56:02,200 --> 03:56:04,560 [APPLAUSE] 5742 03:56:04,560 --> 03:56:13,200 5743 03:56:13,200 --> 03:56:13,960 >> FANTASTIC. 5744 03:56:13,960 --> 03:56:15,920 IT'S OBVIOUS FROM THE 5745 03:56:15,920 --> 03:56:16,720 PRESENTATION TRANSFORMATIVE WORK 5746 03:56:16,720 --> 03:56:18,480 NCATS HAS DONE IN THIS SPACE. 5747 03:56:18,480 --> 03:56:21,320 DAN HIMSELF HAS DONE IN LEADING 5748 03:56:21,320 --> 03:56:22,400 THE PROGRAM. 5749 03:56:22,400 --> 03:56:24,160 SO, WE ARE A LITTLE OVER TIME 5750 03:56:24,160 --> 03:56:25,440 BUT THIS IS THE END OF THE DAY 5751 03:56:25,440 --> 03:56:28,280 SO WE'D LOVE TO HAVE A FEW MORE 5752 03:56:28,280 --> 03:56:29,560 MINUTES FOR ADDITIONAL QUESTIONS 5753 03:56:29,560 --> 03:56:30,600 AND COMMENTS. 5754 03:56:30,600 --> 03:56:32,960 ONE QUESTION THAT DID COME IN 5755 03:56:32,960 --> 03:56:34,120 AFTER TYLER'S PRESENTATION THAT 5756 03:56:34,120 --> 03:56:35,960 IS OBVIOUSLY RELEVANT TO DAN'S 5757 03:56:35,960 --> 03:56:37,840 PRESENTATION AS WELL FROM CAROL 5758 03:56:37,840 --> 03:56:40,000 CLARK, WHAT ARE THE DRAW BACKS 5759 03:56:40,000 --> 03:56:41,880 TO USING ORGANS ON A CHIPS AND 5760 03:56:41,880 --> 03:56:43,560 HOW HAS TECHNOLOGY HELPED TO 5761 03:56:43,560 --> 03:56:44,600 REDUCE THIS? 5762 03:56:44,600 --> 03:56:47,440 I THINK THAT'S ALSO RELATED TO 5763 03:56:47,440 --> 03:56:49,080 THE IDEAS AROUND REGULATORY 5764 03:56:49,080 --> 03:56:50,840 QUALIFICATION AND MORE 5765 03:56:50,840 --> 03:56:52,240 WIDESPREAD IMPLEMENTATION WHICH 5766 03:56:52,240 --> 03:56:53,160 WE HOPE TRANSLATIONAL CENTERS 5767 03:56:53,160 --> 03:56:54,440 WILL ADDRESS BUT I WONDER IF YOU 5768 03:56:54,440 --> 03:56:58,400 WANT TO SAY ANYTHING ELSE ABOUT 5769 03:56:58,400 --> 03:56:59,600 EXISTING -- I CAN ASK TYLER IF 5770 03:56:59,600 --> 03:57:07,040 YOU WANT TO UNMUTE AND ADDRESS 5771 03:57:07,040 --> 03:57:08,040 ANY ASPECT OF THAT? 5772 03:57:08,040 --> 03:57:11,640 I DON'T KNOW IF HE'S STILL ON. 5773 03:57:11,640 --> 03:57:11,960 YOU START. 5774 03:57:11,960 --> 03:57:14,120 >> THANK YOU FOR THAT QUESTION. 5775 03:57:14,120 --> 03:57:17,000 IN TERMS OF DRAWBACKS, THE 5776 03:57:17,000 --> 03:57:20,280 TECHNOLOGY CERTAINLY IS STILL IN 5777 03:57:20,280 --> 03:57:22,120 EARLY STAGES, WE ESTABLISHED 5778 03:57:22,120 --> 03:57:24,680 THIS PROGRAM IN 2012, OVER 10 5779 03:57:24,680 --> 03:57:28,280 YEARS OLD, JUST BARELY LEARNING 5780 03:57:28,280 --> 03:57:30,680 HOW TO WALK AND RUN. 5781 03:57:30,680 --> 03:57:35,240 SO THERE ARE STILL TECHNOLOGICAL 5782 03:57:35,240 --> 03:57:35,440 NEEDS. 5783 03:57:35,440 --> 03:57:38,560 IT STILL TAKES -- THE MAIN 5784 03:57:38,560 --> 03:57:40,440 THINGS THAT COMES TO MIND WOULD 5785 03:57:40,440 --> 03:57:42,640 BE LEARNING CURVE, IT WOULD TAKE 5786 03:57:42,640 --> 03:57:44,880 TO PUT -- INCORPORATE INTO THE 5787 03:57:44,880 --> 03:57:45,320 LABORATORIES. 5788 03:57:45,320 --> 03:57:47,040 SO THAT'S WHY EVEN WITH 5789 03:57:47,040 --> 03:57:53,440 COMMERCIAL COMPANIES PUTTING IN 5790 03:57:53,440 --> 03:57:54,680 THOSE NICE PLATFORMS, EMULATE 5791 03:57:54,680 --> 03:57:56,320 AND TISS-USE, IT TAKES A FEW 5792 03:57:56,320 --> 03:57:58,560 MONTHS TO EVEN A YEAR TO GET 5793 03:57:58,560 --> 03:58:00,120 THINGS UP AND RUNNING, AND SO 5794 03:58:00,120 --> 03:58:03,280 WITH THAT IN MIND WE'RE ACTUALLY 5795 03:58:03,280 --> 03:58:07,000 LAUNCHING ANOTHER ASPECT OF OUR 5796 03:58:07,000 --> 03:58:09,760 PROGRAM PROBABLY IN LATE SUMMER, 5797 03:58:09,760 --> 03:58:14,120 IN TERMS OF PROMOTING PLATFORM 5798 03:58:14,120 --> 03:58:15,480 AND INSTRUMENTATION IMPROVEMENTS 5799 03:58:15,480 --> 03:58:18,080 TOWARDS AUTOMATION, TO MAKE IT 5800 03:58:18,080 --> 03:58:20,800 MORE TURNKEY SO YOU CAN RUN THE 5801 03:58:20,800 --> 03:58:23,520 SYSTEM WITH THE PUSH OF A 5802 03:58:23,520 --> 03:58:24,360 BUTTON. 5803 03:58:24,360 --> 03:58:25,160 THAT'S A TECHNOLOGICAL DRAWBACK 5804 03:58:25,160 --> 03:58:27,920 IN TERMS OF THE BIG LEARNING 5805 03:58:27,920 --> 03:58:28,440 CURVE. 5806 03:58:28,440 --> 03:58:30,120 THE OTHER WOULD BE THE BIOLOGY 5807 03:58:30,120 --> 03:58:31,160 SIDE OF THINGS. 5808 03:58:31,160 --> 03:58:37,560 I THINK THE ENGINEERING SIDE CAN 5809 03:58:37,560 --> 03:58:40,720 ALL BE ADDRESSED EVENTUALLY WITH 5810 03:58:40,720 --> 03:58:42,600 INNOVATIONS IN ENGINEERING AND 5811 03:58:42,600 --> 03:58:43,800 PROCESS ENGINEERING BUT WITH THE 5812 03:58:43,800 --> 03:58:46,440 BIOLOGY INHERENT IN THAT IS 5813 03:58:46,440 --> 03:58:48,960 DIVERSITY, YOU KNOW, PROPER 5814 03:58:48,960 --> 03:58:49,960 SOURCING OF CELLS, HOW 5815 03:58:49,960 --> 03:58:52,920 REPRODUCIBLE ARE THE STEM CELLS, 5816 03:58:52,920 --> 03:58:56,320 EVEN FROM PRIMARY DERIVED 5817 03:58:56,320 --> 03:58:56,600 MATERIALS. 5818 03:58:56,600 --> 03:59:00,600 CHECK SITES CAN VARY. 5819 03:59:00,600 --> 03:59:03,120 STANDARDIZING THOSE, CREATING A 5820 03:59:03,120 --> 03:59:05,880 BANK OF PLURIPOTENT STEM CELLS 5821 03:59:05,880 --> 03:59:07,080 FOR CONTROLS AS WELL AS FOR 5822 03:59:07,080 --> 03:59:09,880 PATIENTS WOULD ALSO BE A BIG 5823 03:59:09,880 --> 03:59:12,560 EFFORT THAT NEEDS TO BE 5824 03:59:12,560 --> 03:59:12,800 ADDRESSED. 5825 03:59:12,800 --> 03:59:14,320 AND THEN OF COURSE EVENTUALLY IF 5826 03:59:14,320 --> 03:59:16,800 WE'RE GOING TO USE THIS REALLY 5827 03:59:16,800 --> 03:59:22,040 HAVING A RELIABLE BANK OF 5828 03:59:22,040 --> 03:59:24,920 WELL-DIFFERENTIATED LINES OF 5829 03:59:24,920 --> 03:59:27,000 REPRESENTING VARIOUS LINEAGES OF 5830 03:59:27,000 --> 03:59:28,880 TISSUES AND CELLS THAT CAN BE 5831 03:59:28,880 --> 03:59:32,120 READILY INCORPORATED INTO THESE 5832 03:59:32,120 --> 03:59:33,120 PLATFORMS. 5833 03:59:33,120 --> 03:59:35,960 RIGHT NOW YOU HAVE TO SOURCE OUT 5834 03:59:35,960 --> 03:59:39,440 YOUR OWN STEM CELLS, INDUCE THEM 5835 03:59:39,440 --> 03:59:41,880 TO PLURIPOTENCY AND OF COURSE 5836 03:59:41,880 --> 03:59:42,640 DEVELOP DIFFERENTIATION 5837 03:59:42,640 --> 03:59:43,400 PROCEDURES FOR YOUR VARIOUS 5838 03:59:43,400 --> 03:59:45,720 TISSUE TIMES THAT YOU WANT TO 5839 03:59:45,720 --> 03:59:48,200 STUDY, AND THEN BE ABLE TO SEED 5840 03:59:48,200 --> 03:59:51,720 THEM INTO YOUR PLATFORM SO THOSE 5841 03:59:51,720 --> 03:59:53,440 ARE LIKE THE -- I WOULD CONSIDER 5842 03:59:53,440 --> 03:59:57,400 TO BE THE MAJOR DRAWBACKS. 5843 03:59:57,400 --> 03:59:58,840 5844 03:59:58,840 --> 04:00:00,280 >> THANKS, DAN. 5845 04:00:00,280 --> 04:00:02,760 THAT WAS IMPRESSIVE TALK. 5846 04:00:02,760 --> 04:00:04,200 QUESTION ABOUT YOU MENTIONED 5847 04:00:04,200 --> 04:00:07,560 COLLABORATIONS WITH SO MANY 5848 04:00:07,560 --> 04:00:09,000 DIFFERENT ORGANIZATIONS, 5849 04:00:09,000 --> 04:00:11,960 AGENCIES, AND IN ADDITION TO THE 5850 04:00:11,960 --> 04:00:13,600 HIGHER LEVEL BIG PICTURE 5851 04:00:13,600 --> 04:00:15,760 ENGAGEMENT AND SUPPORT FOR THESE 5852 04:00:15,760 --> 04:00:17,400 PROJECTS IS THAT TRICKLING DOWN 5853 04:00:17,400 --> 04:00:21,040 TO THE REVIEWER LEVEL, SO 5854 04:00:21,040 --> 04:00:22,600 TAKING, FOR EXAMPLE, THE SANOFI 5855 04:00:22,600 --> 04:00:25,080 SUBMISSION YOU MENTIONED, WHEN 5856 04:00:25,080 --> 04:00:27,720 THAT REVIEWER IN FDA OR EMA OR 5857 04:00:27,720 --> 04:00:29,920 OTHER AGENCY GETS THE SUBMISSION 5858 04:00:29,920 --> 04:00:31,120 DO THEY KNOW WHAT TO DO WITH IT 5859 04:00:31,120 --> 04:00:32,680 AND HOW TO INTERPRET THE DATA? 5860 04:00:32,680 --> 04:00:33,960 >>YEAH, THAT'S A GOOD POINT. 5861 04:00:33,960 --> 04:00:38,320 COMING FROM THE NIH WHEN WE TALK 5862 04:00:38,320 --> 04:00:40,720 ABOUT PEER REVIEW, YOU'RE 5863 04:00:40,720 --> 04:00:41,920 TALKING ABOUT REGULATORY REVIEW, 5864 04:00:41,920 --> 04:00:43,120 SO CERTAINLY THAT'S A 5865 04:00:43,120 --> 04:00:44,960 RECOGNITION THAT WE HAVE HAD IN 5866 04:00:44,960 --> 04:00:48,600 THE VERY BEGINNING OF THE 5867 04:00:48,600 --> 04:00:52,880 PROGRAM, WAY BACK IN 2009, EVEN 5868 04:00:52,880 --> 04:00:54,840 PRECEDING THE TISSUE CHIP 5869 04:00:54,840 --> 04:00:55,720 PROGRAM, WITH MY OFFICE, MY 5870 04:00:55,720 --> 04:00:58,680 GROUP HAS BEEN WORKING WITH THE 5871 04:00:58,680 --> 04:00:59,640 FDA PRIMARILY AS REGULATORY 5872 04:00:59,640 --> 04:01:03,840 AGENCY TO MAKE SURE THAT THEY 5873 04:01:03,840 --> 04:01:05,400 ARE AWARE OF THESE DEVELOPMENTS, 5874 04:01:05,400 --> 04:01:07,440 SO WE'VE BEEN WORKING WITH THEM 5875 04:01:07,440 --> 04:01:11,160 SINCE 2012 WHEN THE PROGRAM WAS 5876 04:01:11,160 --> 04:01:12,280 INITIALLY -- CAME INTO 5877 04:01:12,280 --> 04:01:13,280 INCEPTION, AND SINCE THEN WE'VE 5878 04:01:13,280 --> 04:01:15,920 HAD A NUMBER OF WORKSHOPS WITH 5879 04:01:15,920 --> 04:01:20,680 THE FDA, WITHIN THE FDA, AND 5880 04:01:20,680 --> 04:01:23,440 RECENTLY FDA OF COURSE HAS SET 5881 04:01:23,440 --> 04:01:25,080 UP THEIR OWN LABORATORIES TO 5882 04:01:25,080 --> 04:01:26,600 UNDERSTAND WHAT THE TECHNOLOGY 5883 04:01:26,600 --> 04:01:28,360 IS ABOUT, UNDERSTAND WHERE 5884 04:01:28,360 --> 04:01:29,600 LIMITATIONS ARE, WHERE THE GAPS 5885 04:01:29,600 --> 04:01:32,440 ARE, AS WELL AS WHERE THE 5886 04:01:32,440 --> 04:01:33,720 OPPORTUNITIES ARE. 5887 04:01:33,720 --> 04:01:38,000 AND PART OF THAT IS ALSO 5888 04:01:38,000 --> 04:01:43,680 CREATING GLOBAL COMMUNITY THAT 5889 04:01:43,680 --> 04:01:44,240 REGULATORY AGENCIES, THE 5890 04:01:44,240 --> 04:01:48,960 REVIEWERS, CAN ENTER AC -- 5891 04:01:48,960 --> 04:01:50,080 INTERACT AND INTERFACE WITH 5892 04:01:50,080 --> 04:01:50,960 DEVELOPERS. 5893 04:01:50,960 --> 04:01:53,680 THAT'S THE FRAMEWORK WE HAD IN 5894 04:01:53,680 --> 04:01:56,160 MIND WHEN WE ESTABLISHED TISSUE 5895 04:01:56,160 --> 04:01:57,440 CHIP PROGRAM, CONSORTIUM OF 5896 04:01:57,440 --> 04:02:00,120 INVESTIGATORS, ON A MONTHLY 5897 04:02:00,120 --> 04:02:03,200 BASIS, AT LEAST ON CALLS, IN 5898 04:02:03,200 --> 04:02:04,400 PERSON, SEMI ANNUAL BASIS, WOULD 5899 04:02:04,400 --> 04:02:06,240 BE INTERACTING WITH THE FDA. 5900 04:02:06,240 --> 04:02:10,760 AND SO THEY ARE GOING TO BE 5901 04:02:10,760 --> 04:02:12,200 WORKING WITH THEM ALONGSIDE. 5902 04:02:12,200 --> 04:02:14,280 FOR EXAMPLE, THE TRANSLATIONAL 5903 04:02:14,280 --> 04:02:15,880 CENTERS THAT I MENTIONED, IT'S 5904 04:02:15,880 --> 04:02:19,080 ACTUALLY IN PARTNERSHIP WITH THE 5905 04:02:19,080 --> 04:02:19,520 FDA. 5906 04:02:19,520 --> 04:02:21,120 WE HAVE, YOU KNOW, THIS WAS 5907 04:02:21,120 --> 04:02:26,160 SOMETHING THAT DEVELOPED EVEN 5908 04:02:26,160 --> 04:02:31,360 TWO YEARS AGO WHEN JANET WILCOCK 5909 04:02:31,360 --> 04:02:34,600 WAS ACTING COMMISSIONER OF FDA 5910 04:02:34,600 --> 04:02:38,360 SO IN TERMS OF ACTIVITIES WITH 5911 04:02:38,360 --> 04:02:41,640 THIS WOULD BE ALONG ACTIVE FDA 5912 04:02:41,640 --> 04:02:43,720 ENGAGEMENT SO THAT ANY CENTER 5913 04:02:43,720 --> 04:02:47,960 THAT WE FUND AT THE NIH WOULD 5914 04:02:47,960 --> 04:02:49,160 HAVE FDA REGULATORS COMING 5915 04:02:49,160 --> 04:02:52,320 ALONGSIDE THEM AND ADVISING THEM 5916 04:02:52,320 --> 04:02:53,680 IN TERMS OF WHAT THE PLATFORMS 5917 04:02:53,680 --> 04:02:55,640 ARE GOING TO BE THAT'S GOING TO 5918 04:02:55,640 --> 04:02:57,280 BE QUALIFIED FOR SPECIFIC 5919 04:02:57,280 --> 04:02:58,680 CONTEXT OF USE. 5920 04:02:58,680 --> 04:03:01,200 YEAH, SO THAT'S PART OF THE 5921 04:03:01,200 --> 04:03:01,480 THINGS. 5922 04:03:01,480 --> 04:03:04,800 WE HAVE WORKED WITH THE 5923 04:03:04,800 --> 04:03:07,240 REGULATORY SUMMIT AS WELL, THAT 5924 04:03:07,240 --> 04:03:10,720 WAS MPS WAS THE SUBJECT OF THE 5925 04:03:10,720 --> 04:03:13,040 REGULATORY SUMMIT IN TERMS OF 5926 04:03:13,040 --> 04:03:15,760 EMERGING TECHNOLOGY I THINK IN 5927 04:03:15,760 --> 04:03:18,440 2022 OR 2021, YEAH, SO THERE'S 5928 04:03:18,440 --> 04:03:25,400 CONSTANT ENGAGEMENT. 5929 04:03:25,400 --> 04:03:26,280 THANK YOU. 5930 04:03:26,280 --> 04:03:27,040 >> GREAT TALK. 5931 04:03:27,040 --> 04:03:32,080 ENJOYED THAT VERY MUCH. 5932 04:03:32,080 --> 04:03:33,480 A COUPLE QUESTIONS, NOT 5933 04:03:33,480 --> 04:03:34,600 NECESSARILY FOR US TO ANSWER 5934 04:03:34,600 --> 04:03:39,000 TODAY, BUT HOW IS THIS GOING TO 5935 04:03:39,000 --> 04:03:40,200 BE SCALABLE? 5936 04:03:40,200 --> 04:03:45,000 IS ONE CHIP EQUIVALENT TO ONE 5937 04:03:45,000 --> 04:03:46,840 ANIMAL OR ONE HUMAN SO IF WE'RE 5938 04:03:46,840 --> 04:03:51,880 RUNNING A CLINICAL TRIAL ON A 5939 04:03:51,880 --> 04:03:54,960 CHIP DO YOU NEED TENS OR IF 5940 04:03:54,960 --> 04:03:57,120 YOU'RE DOING TOX TESTING WOULD 5941 04:03:57,120 --> 04:03:58,560 YOU NEED HUNDREDS OF CHIPS TO BE 5942 04:03:58,560 --> 04:04:01,920 ABLE TO SCALE THIS UP? 5943 04:04:01,920 --> 04:04:06,160 >>YEAH, I JUST CAME BACK FROM A 5944 04:04:06,160 --> 04:04:07,320 TISSUE MODEL CONFERENCE IN 5945 04:04:07,320 --> 04:04:07,720 BOSTON. 5946 04:04:07,720 --> 04:04:11,600 THAT WAS A BIG DISCUSSION. 5947 04:04:11,600 --> 04:04:13,600 HOW DO WE REPRESENT AN ENTIRE 5948 04:04:13,600 --> 04:04:17,840 ORGANISM ON A CHIP? 5949 04:04:17,840 --> 04:04:19,360 THE ANSWER, IT DEPENDS ON THE 5950 04:04:19,360 --> 04:04:21,440 BIOLOGICAL QUESTION YOU'RE 5951 04:04:21,440 --> 04:04:25,400 TRYING TO ANSWER. 5952 04:04:25,400 --> 04:04:26,160 MY PHILOSOPHY IS DON'T 5953 04:04:26,160 --> 04:04:27,000 OVERBUILD, JUST DEVELOP 5954 04:04:27,000 --> 04:04:29,000 SOMETHING THAT WOULD ANSWER THE 5955 04:04:29,000 --> 04:04:31,200 BIOLOGICAL QUESTION YOU HAVE. 5956 04:04:31,200 --> 04:04:33,240 SO THERE ARE PARTICULAR 5957 04:04:33,240 --> 04:04:35,480 BIOLOGICAL QUESTIONS THAT WOULD 5958 04:04:35,480 --> 04:04:38,200 BE SUFFICIENT TO ANSWER WITH A 5959 04:04:38,200 --> 04:04:40,520 SINGLE ORGAN CHIP, COULD BE 5960 04:04:40,520 --> 04:04:41,520 MULTI-ORGAN CHIP AS WELL, SO 5961 04:04:41,520 --> 04:04:46,880 THAT WOULD STILL BE ONE CHIP BUT 5962 04:04:46,880 --> 04:04:49,400 IF YOUR QUESTION INVOLVES 5963 04:04:49,400 --> 04:04:51,160 POPULATION VARIATION, 5964 04:04:51,160 --> 04:04:53,560 DIFFERENCES IN RESPONSE, RISK, 5965 04:04:53,560 --> 04:04:55,720 ESSENTIALLY MULTI-ORGAN CHIPS, 5966 04:04:55,720 --> 04:04:58,040 MANY CHIPS, AND MANY, MANY CELL 5967 04:04:58,040 --> 04:05:02,280 SOURCES AS WELL. 5968 04:05:02,280 --> 04:05:02,800 THAT GROWS EXPONENTIALLY 5969 04:05:02,800 --> 04:05:03,720 DEPENDING ON THE TYPE OF 5970 04:05:03,720 --> 04:05:04,000 QUESTIONS. 5971 04:05:04,000 --> 04:05:05,560 >> THE NEXT QUESTION IS WHO IS 5972 04:05:05,560 --> 04:05:09,720 GOING TO PAY FOR THIS? 5973 04:05:09,720 --> 04:05:11,520 IT'S ONE THING FOR US THAT ARE 5974 04:05:11,520 --> 04:05:12,560 BLESSED TO WORK WITHIN THE 5975 04:05:12,560 --> 04:05:15,880 FEDERAL GOVERNMENT AND HAVE 5976 04:05:15,880 --> 04:05:17,160 THESE RESOURCES, IN PARTICULAR 5977 04:05:17,160 --> 04:05:19,240 NCATS WITH THE AUTOMATION AND 5978 04:05:19,240 --> 04:05:20,920 INCREDIBLE RESOURCES THAT YOU 5979 04:05:20,920 --> 04:05:25,400 HAVE THERE, HOW IS THIS GOING TO 5980 04:05:25,400 --> 04:05:28,320 BE AFFORDABLE TO THE INDUSTRY 5981 04:05:28,320 --> 04:05:30,760 AND FOR CROs TO VENTURE INTO 5982 04:05:30,760 --> 04:05:33,360 THIS AREA AND OPERATE AS A 5983 04:05:33,360 --> 04:05:33,600 SERVICE? 5984 04:05:33,600 --> 04:05:35,440 >> RIGHT, YES. 5985 04:05:35,440 --> 04:05:36,280 THERE'S ESSENTIALLY APPROACHES 5986 04:05:36,280 --> 04:05:39,520 TO SCALE UP IN MANUFACTURING. 5987 04:05:39,520 --> 04:05:44,680 MOST OF THIS, COMMERCIAL 5988 04:05:44,680 --> 04:05:46,320 COMPANIES ARE ESSENTIALLY 5989 04:05:46,320 --> 04:05:47,960 EXISTING TO MANUFACTURE THEM, 5990 04:05:47,960 --> 04:05:49,560 AND COMMERCIALIZE THEM. 5991 04:05:49,560 --> 04:05:50,960 THEY ARE STILL EXPENSIVE BECAUSE 5992 04:05:50,960 --> 04:05:53,000 IT HASN'T GONE INTO THE LARGE 5993 04:05:53,000 --> 04:05:53,600 SCALE MANUFACTURING. 5994 04:05:53,600 --> 04:05:57,040 I THINK THAT'S WHERE THE 5995 04:05:57,040 --> 04:05:58,000 STANDARDS AND QUALIFICATION DRUG 5996 04:05:58,000 --> 04:06:01,040 DEVELOPMENT TOOLS WILL COME IN 5997 04:06:01,040 --> 04:06:03,640 BECAUSE ONCE QUALIFIED, I THINK 5998 04:06:03,640 --> 04:06:04,240 LARGE MANUFACTURERS WOULD THEN 5999 04:06:04,240 --> 04:06:06,920 SAY THERE IS GOING TO BE A HUGE 6000 04:06:06,920 --> 04:06:09,440 MARKET SHARE FOR THIS. 6001 04:06:09,440 --> 04:06:11,640 AND SO THEY CAN ESSENTIALLY STEP 6002 04:06:11,640 --> 04:06:15,120 IN AND PRODUCE THOUSANDS IF NOT 6003 04:06:15,120 --> 04:06:18,080 MILLIONS OF CHIPS. 6004 04:06:18,080 --> 04:06:18,840 THAT SHOULD TECHNICALLY DRIVE 6005 04:06:18,840 --> 04:06:22,160 DOWN THE COST OF THIS 6006 04:06:22,160 --> 04:06:24,320 TECHNOLOGY, ESPECIALLY IF WE ARE 6007 04:06:24,320 --> 04:06:28,400 ABLE TO ADDRESS THE ISSUE OF 6008 04:06:28,400 --> 04:06:31,080 AUTOMATION, BECAUSE THAT'S A BIG 6009 04:06:31,080 --> 04:06:31,560 THING. 6010 04:06:31,560 --> 04:06:34,680 IT'S ONE -- THOSE ARE 6011 04:06:34,680 --> 04:06:36,960 CONSUMABLES BUT THE PLATFORM OR 6012 04:06:36,960 --> 04:06:38,080 THE SUPPORTING INSTRUMENTATION 6013 04:06:38,080 --> 04:06:41,080 CAN BE A ONE-TIME EXPENSE BUT 6014 04:06:41,080 --> 04:06:43,480 THERE'S A LARGE ACQUISITION COST 6015 04:06:43,480 --> 04:06:47,400 THAT YOU NEED TO INVEST IN, AND 6016 04:06:47,400 --> 04:06:49,360 NOT EVERY LABORATORY IS ABLE 6017 04:06:49,360 --> 04:06:51,120 TO -- UNLESS THEY HAVE AN 6018 04:06:51,120 --> 04:06:52,120 INSTRUMENTATION GRANT FROM THE 6019 04:06:52,120 --> 04:06:55,080 NIH, BUT OUR GOAL IS TO MAKE 6020 04:06:55,080 --> 04:06:57,240 THIS SORT OF LIKE YOUR PCR 6021 04:06:57,240 --> 04:07:00,400 MACHINE THAT CAN SIT ON EVERY 6022 04:07:00,400 --> 04:07:02,400 BENCH TOP AND PLUG IN YOUR CHIPS 6023 04:07:02,400 --> 04:07:04,920 AND RUN YOUR EXPERIMENTS AND 6024 04:07:04,920 --> 04:07:07,080 WALK AWAY, TO GO TO A COFFEE 6025 04:07:07,080 --> 04:07:09,520 BREAK, OR LUNCH BREAK, AS WE'RE 6026 04:07:09,520 --> 04:07:14,440 HEADING NOW. 6027 04:07:14,440 --> 04:07:14,560 6028 04:07:14,560 --> 04:07:17,960 >> THANK YOU ALL SO MUCH. 6029 04:07:17,960 --> 04:07:20,960 SO WE'VE REACHED THE END OF OUR 6030 04:07:20,960 --> 04:07:23,200 PROGRAM NOW. 6031 04:07:23,200 --> 04:07:25,600 I DO WANT TO READ A GENERAL 6032 04:07:25,600 --> 04:07:29,200 COMMENT WE GOT FROM AMY KYLE 6033 04:07:29,200 --> 04:07:31,320 THAT I THINK REFLECTS ONE OF THE 6034 04:07:31,320 --> 04:07:32,560 THINGS I WANTED TO MENTION. 6035 04:07:32,560 --> 04:07:34,240 SHE SAID I WANT TO THANK THE 6036 04:07:34,240 --> 04:07:35,880 SUPPORT GROUP FOR MAKING IT 6037 04:07:35,880 --> 04:07:38,520 POSSIBLE TO PARTICIPATE IN THIS 6038 04:07:38,520 --> 04:07:40,240 EVENT AND THANK NICEATM FOR 6039 04:07:40,240 --> 04:07:41,040 ENTERTAINING COMMENTS FROM 6040 04:07:41,040 --> 04:07:42,240 OUTSIDE IN A MEANINGFUL WAY. 6041 04:07:42,240 --> 04:07:44,080 I APPRECIATE YOUR WORK AND 6042 04:07:44,080 --> 04:07:45,520 THOUGHTFULNESS VERY MUCH. 6043 04:07:45,520 --> 04:07:48,480 THANK YOU FOR THOSE POSITIVE 6044 04:07:48,480 --> 04:07:48,800 COMMENTS. 6045 04:07:48,800 --> 04:07:52,320 AND THEY REFLECT HOW I FEEL 6046 04:07:52,320 --> 04:07:54,720 ABOUT THE SUPPORT THAT HAS BEEN 6047 04:07:54,720 --> 04:07:58,440 PROVIDED FROM BOTH OUR SUPPORT 6048 04:07:58,440 --> 04:08:00,960 CONTRACTORS AND ALSO AV SUPPORT 6049 04:08:00,960 --> 04:08:04,080 TEAM HERE AT THE NIH BETHESDA 6050 04:08:04,080 --> 04:08:10,120 CENTER, I WANT TO THANK IN 6051 04:08:10,120 --> 04:08:12,080 PARTICULAR STEPHEN MOREFIELD, 6052 04:08:12,080 --> 04:08:15,840 CATHY SPRANGEL AND DAVE ALLEN 6053 04:08:15,840 --> 04:08:16,840 FOR THEIR LEADERSHIP MAKING SURE 6054 04:08:16,840 --> 04:08:18,840 THIS HAPPENED AND I DIDN'T GO 6055 04:08:18,840 --> 04:08:20,120 CRAZY IN THE PROCESS. 6056 04:08:20,120 --> 04:08:23,640 WHICH THAT'S UP FOR DEBATE 6057 04:08:23,640 --> 04:08:24,560 PROBABLY. 6058 04:08:24,560 --> 04:08:30,280 BUT IF I COULD STOP SHARING 6059 04:08:30,280 --> 04:08:30,720 THIS, OKAY. 6060 04:08:30,720 --> 04:08:33,480 SO, AGAIN, THANK YOU ALL. 6061 04:08:33,480 --> 04:08:35,840 THIS CONCLUDES AND INCREDIBLY 6062 04:08:35,840 --> 04:08:36,680 INFORMATIVE AND PRODUCTIVE AND 6063 04:08:36,680 --> 04:08:39,280 EXCITING TWO DAYS OF THE ICCVAM 6064 04:08:39,280 --> 04:08:40,600 PUBLIC FORUM. 6065 04:08:40,600 --> 04:08:42,280 I CERTAINLY HAVE A THOUSAND 6066 04:08:42,280 --> 04:08:46,040 IDEAS IN MY HEAD TO RUMINATE AND 6067 04:08:46,040 --> 04:08:47,600 FOLLOW UP ON. 6068 04:08:47,600 --> 04:08:48,840 I'LL LEAVE IT TO DR. GORDON TO 6069 04:08:48,840 --> 04:08:51,760 SEE IF HE WANTS TO SAY ANYTHING 6070 04:08:51,760 --> 04:08:52,080 IN CLOSING. 6071 04:08:52,080 --> 04:08:52,280 NO? 6072 04:08:52,280 --> 04:08:55,080 YOU'RE HAPPY FOR ME TO CLOUT 6073 04:08:55,080 --> 04:08:57,760 OUT? 6074 04:08:57,760 --> 04:08:58,520 ALL RIGHT, JOHN. 6075 04:08:58,520 --> 04:09:00,120 THANK YOU FOR COMING IN PERSON. 6076 04:09:00,120 --> 04:09:01,720 A DELIGHT TO SEE YOU ALL. 6077 04:09:01,720 --> 04:09:02,960 THANKS TO EVERYBODY ON THE 6078 04:09:02,960 --> 04:09:04,440 WEBCAST FOR TAKING SO MUCH TIME 6079 04:09:04,440 --> 04:09:06,440 OUT OF YOUR BUSY SCHEDULES TO 6080 04:09:06,440 --> 04:09:07,560 SPEND WITH US. 6081 04:09:07,560 --> 04:09:09,160 AND WE'LL LOOK FORWARD TO NEXT 6082 04:09:09,160 --> 04:09:11,040 YEAR AND LOTS OF FOLLOW-UP 6083 04:09:11,040 --> 04:09:13,120 ACTIVITIES IN BETWEEN. 6084 04:09:13,120 --> 04:09:14,240 THANKS, EVERYONE. 6085 04:09:14,240 --> 00:00:00,000 [APPLAUSE]