1 00:00:05,520 --> 00:00:08,840 >> WE WELCOME YOU 2 00:00:08,840 --> 00:00:10,720 TO WHAT SURELY WILL BE AN 3 00:00:10,720 --> 00:00:15,800 EXCITING AND STIMULATING 4 00:00:15,800 --> 00:00:17,400 PRESENTATION. AND RAISE YOUR 5 00:00:17,400 --> 00:00:22,120 SIGHTS TO ISSUES IN BIOLOGY THAT 6 00:00:22,120 --> 00:00:24,440 OFTEN EXCEED THOSE AT THE LEVEL 7 00:00:24,440 --> 00:00:26,400 AT WHICH WE NORMALLY WORK 8 00:00:26,400 --> 00:00:27,680 WHETHER MORE CLINICALLY OR EVEN 9 00:00:27,680 --> 00:00:31,200 IN THE LABORATORY. SO THIS 10 00:00:31,200 --> 00:00:34,800 PROGRAM IS ACTUALLY TRIPLY 11 00:00:34,800 --> 00:00:37,320 SPONSORED BY THE FAES WHICH 12 00:00:37,320 --> 00:00:40,600 KINDLY IS GOING TO SPONSOR A 13 00:00:40,600 --> 00:00:43,560 RECEPTION AT THE END OF TODAY'S 14 00:00:43,560 --> 00:00:48,680 SESSION IN THE RECEPTION AREA 15 00:00:48,680 --> 00:00:51,720 AROUND HERE. AND IN ADDITION IT 16 00:00:51,720 --> 00:00:55,120 IS SPONSORED BY THE INTRAMURAL 17 00:00:55,120 --> 00:00:59,640 PROGRAM OF THE NIH. AND BY THE 18 00:00:59,640 --> 00:01:01,400 DEMYSTIFYING MEDICINE COURSE. 19 00:01:01,400 --> 00:01:04,120 LET ME SAY A WORD ABOUT THAT. 20 00:01:04,120 --> 00:01:06,920 THOSE OF YOU WHO IF THERE ARE 21 00:01:06,920 --> 00:01:08,440 ANY WHO HAVE NEVER BEEN TO ANY 22 00:01:08,440 --> 00:01:12,320 OF OUR SESSIONS I WOULD TELL YOU 23 00:01:12,320 --> 00:01:17,360 THAT THIS COURSE IS NOW ENDING 24 00:01:17,360 --> 00:01:20,000 ITS 23RD YEAR. ITS GOAL IS TO 25 00:01:20,000 --> 00:01:21,960 BRIDGE EXCITING DEVELOPMENTS IN 26 00:01:21,960 --> 00:01:23,200 BIOLOGY AND ENGINEERING WITH 27 00:01:23,200 --> 00:01:26,960 MEDICINE. NORMALLY IT IS ON 28 00:01:26,960 --> 00:01:29,840 TUESDAYS FROM 4 TO 6 FROM 29 00:01:29,840 --> 00:01:32,480 JANUARY TO SOMETIME IN MAY. AND 30 00:01:32,480 --> 00:01:36,480 IT CAN BE WATCHED ON THE NIH 31 00:01:36,480 --> 00:01:38,080 VIDEOCAST, THIS YEAR IT WAS ALL 32 00:01:38,080 --> 00:01:40,600 VIRTUAL AND WE HAD ATTENDANCE 33 00:01:40,600 --> 00:01:43,360 RANGING UP INTO THE THOUSANDS 34 00:01:43,360 --> 00:01:46,840 BECAUSE IT GOES GLOBALLY. MANY 35 00:01:46,840 --> 00:01:50,400 OF OUR PARTICIPANTS WERE GLOBAL 36 00:01:50,400 --> 00:01:51,920 WHEREAS IN PREVIOUS YEARS 37 00:01:51,920 --> 00:01:55,320 EVERYONE WAS HERE ON SITE. WE 38 00:01:55,320 --> 00:01:57,000 THINK NEXT YEAR THE PROGRAM WILL 39 00:01:57,000 --> 00:02:00,440 BE A HYBRID ONE INCORPORATED BY 40 00:02:00,440 --> 00:02:01,920 ASPECTS. 41 00:02:01,920 --> 00:02:03,480 THE PICTURE IN THE UPPER RIGHT 42 00:02:03,480 --> 00:02:05,680 IS WHAT MANY OF US IN EAST OF 43 00:02:05,680 --> 00:02:08,040 THE ROCKY MOUNTAINS THINK IS THE 44 00:02:08,040 --> 00:02:09,000 GREATEST BRIDGE IN THE WORLD. 45 00:02:09,000 --> 00:02:11,080 THAT'S THE BROOKLYN BRIDGE. AND 46 00:02:11,080 --> 00:02:13,880 THE REASON WE SHOW IT IS BECAUSE 47 00:02:13,880 --> 00:02:16,400 THE WHO GENERALMEN ON THE CAT 48 00:02:16,400 --> 00:02:20,080 WALK ARE ESSENTIALLY BRIDGING. 49 00:02:20,080 --> 00:02:23,720 SO FOR TODAY, OUR SPEAKER IS AN 50 00:02:23,720 --> 00:02:25,520 EVOLUTIONARY BIOCHEMIST AND WE 51 00:02:25,520 --> 00:02:28,080 ARE ONE OF THOSE INDIVIDUALS WHO 52 00:02:28,080 --> 00:02:31,600 ARE GOING TO LISTEN, LEARN, 53 00:02:31,600 --> 00:02:35,520 THINK AND MAYBE INFLUENCE SOME 54 00:02:35,520 --> 00:02:44,960 OF OUR EXPERIMENTAL WORKS. THIS 55 00:02:44,960 --> 00:02:45,880 IS ESSENTIALLY IN BRIDGE 56 00:02:45,880 --> 00:02:48,120 BUILDING. NORMALLY WE TRIED TO 57 00:02:48,120 --> 00:02:50,120 HAVE A LIVE PATIENT, A CLINICAL 58 00:02:50,120 --> 00:02:54,560 -- CLINICIAN, INVESTIGATOR AND 59 00:02:54,560 --> 00:02:58,160 BASIC SCIENTIST WHO SHARE NOT 60 00:02:58,160 --> 00:03:00,160 LAST WE CAN'S RESEARCH SEMINAR 61 00:03:00,160 --> 00:03:03,320 BUT ONE OF THE BIG CHALLENGING 62 00:03:03,320 --> 00:03:06,400 THAT CONFRONT THE TOPIC AT HAND. 63 00:03:06,400 --> 00:03:08,960 MANY TIMES WE ARE FORTUNATE BY 64 00:03:08,960 --> 00:03:10,520 HAVING ESSENTIALLY A SINGLE 65 00:03:10,520 --> 00:03:13,840 SPEAKER SUCH AS TODAY. BECAUSE 66 00:03:13,840 --> 00:03:15,400 THE BRIDGES THAT THOSE PEOPLE 67 00:03:15,400 --> 00:03:17,640 ARE INVOLVED IN ARE QUITE 68 00:03:17,640 --> 00:03:20,400 DIFFERENT FROM THE ONES WE 69 00:03:20,400 --> 00:03:23,280 NORMALLY CONSIDER AT BENCH TO 70 00:03:23,280 --> 00:03:25,040 BEDSIDE. SO WE HAVE HAD SPEAKERS 71 00:03:25,040 --> 00:03:29,680 FROM NASA TALK ABOUT BIOLOGY AND 72 00:03:29,680 --> 00:03:31,440 SPACE, WE HAVE HAD SPEAKERS FROM 73 00:03:31,440 --> 00:03:35,240 THE OCEAN GRAPHIC TALK ABOUT 74 00:03:35,240 --> 00:03:38,160 BIOLOGY ON THE SEA FLOOR, AND A 75 00:03:38,160 --> 00:03:44,280 GREAT VARIETY OF BIG BRIDGERS IN 76 00:03:44,280 --> 00:03:45,840 BIOLOGY ALL OF THOSE SPIN OFF TO 77 00:03:45,840 --> 00:03:47,880 MEDICINE. OKAY. ENOUGH. SO 78 00:03:47,880 --> 00:03:50,600 TODAY'S SPEAKER YOU KNOW IS NICK 79 00:03:50,600 --> 00:03:52,320 LANE, WHO I SUSPECT IS WELL 80 00:03:52,320 --> 00:03:56,600 KNOWN TO ALL OF YOU. LARGELY 81 00:03:56,600 --> 00:03:58,560 BECAUSE OF HIS RESEARCH AND 82 00:03:58,560 --> 00:04:01,920 PARTICULARLY HIS BOOKS. I BRING 83 00:04:01,920 --> 00:04:03,440 YOUR ATTENTION THERE WILL BE A 84 00:04:03,440 --> 00:04:05,560 BOOK SIGNING AT THE CONCLUSION 85 00:04:05,560 --> 00:04:10,520 OF TODAY'S PROGRAM OF NICK'S 86 00:04:10,520 --> 00:04:13,800 FIFTH BOOK CALLED TRANSFORMING. 87 00:04:13,800 --> 00:04:14,920 MAY WE HAVE THE NEXT SLIDE 88 00:04:14,920 --> 00:04:22,520 PLEASE. THANK YOU. SO NICK IS 89 00:04:22,520 --> 00:04:25,400 PROFESSOR OF EVOLUTIONARY 90 00:04:25,400 --> 00:04:26,400 BIOCHEMISTRY IN THE DEPARTMENT 91 00:04:26,400 --> 00:04:28,400 OF GENETICS, EVOLUTION AND 92 00:04:28,400 --> 00:04:29,880 ENVIRONMENT AT THE UNIVERSITY 93 00:04:29,880 --> 00:04:33,760 COLLEGE LONDON IN THE UK. HIS 94 00:04:33,760 --> 00:04:35,160 RESEARCH THROUGH THE YEARS HAS 95 00:04:35,160 --> 00:04:36,960 CONCERNED MAJOR ISSUES LIKE THE 96 00:04:36,960 --> 00:04:39,480 ORIGIN OF LIFE, THE ORIGIN OF 97 00:04:39,480 --> 00:04:42,600 THE EUKARYOTIC CELL, THE ORIGIN 98 00:04:42,600 --> 00:04:50,480 OF SEX OF SPECIESATION, AND 99 00:04:50,480 --> 00:04:52,040 AGING, NOT SO MUCH TO GENOMICS 100 00:04:52,040 --> 00:04:57,000 AS RELATED TO BIOENERGETICS. 101 00:04:57,000 --> 00:05:00,800 THE ENERGY THAT PRESUMABLY 102 00:05:00,800 --> 00:05:04,000 PRECEDES THE GENOME. DOES IT? WE 103 00:05:04,000 --> 00:05:05,360 WILL HEAR DISCUSSION OF THAT. 104 00:05:05,360 --> 00:05:10,320 NICK IS FOUNDER OF IT WILL 105 00:05:10,320 --> 00:05:13,080 COLLEGE OF LONDON CONSORTIUM FOR 106 00:05:13,080 --> 00:05:14,200 MITOCHONDRIAL RESEARCH AND FOR 107 00:05:14,200 --> 00:05:17,520 THE RESEARCH FRONTIERS ORIGIN OF 108 00:05:17,520 --> 00:05:20,480 LIFE PROGRAM AT THAT UNIVERSITY 109 00:05:20,480 --> 00:05:25,880 HE TEACHES ENERGY AND EVOLUTION 110 00:05:25,880 --> 00:05:27,240 TO WHICH I'M SURE ARE VERY 111 00:05:27,240 --> 00:05:28,920 EXCITED STUDENTS. AND WELL KNOWN 112 00:05:28,920 --> 00:05:31,880 IS HE IS AUTHOR OF FIVE 113 00:05:31,880 --> 00:05:33,480 ACCLAIMED BOOKS ON EVOLUTIONARY 114 00:05:33,480 --> 00:05:36,960 BIOCHEMISTRY. THIS IF YOU HAVE 115 00:05:36,960 --> 00:05:39,120 NEVER READ ANY OF HIS BOOKS YOU 116 00:05:39,120 --> 00:05:40,760 SHOULD READ ANY ONE OF THEM 117 00:05:40,760 --> 00:05:43,080 BECAUSE THEY CONVERT 118 00:05:43,080 --> 00:05:44,920 BIOCHEMISTRY FROM SOMETHING LIKE 119 00:05:44,920 --> 00:05:48,000 A COMPLEX PATHWAY OF THINGS 120 00:05:48,000 --> 00:05:50,200 INTERACTING IN AN IMPOSSIBLE 121 00:05:50,200 --> 00:05:52,320 SCENARIO TO UNDERSTAND, 122 00:05:52,320 --> 00:05:55,720 CONVERTED INTO DYNAMIC, WHAT IS 123 00:05:55,720 --> 00:05:58,960 GOING ON EVERY SECOND IF NOT 124 00:05:58,960 --> 00:06:00,720 MILLISECOND WITHIN OUR CELLS. 125 00:06:00,720 --> 00:06:02,640 HIS MOST RECENT BOOK IS 126 00:06:02,640 --> 00:06:05,080 TRANSFORMER WHICH I MENTIONED. 127 00:06:05,080 --> 00:06:06,720 NICK IS RECEIVED MANY AWARDS 128 00:06:06,720 --> 00:06:10,600 INCLUDING THE ROYAL SOCIETY 129 00:06:10,600 --> 00:06:12,800 PRIZE FOR SCIENCE BOOKS, ONE OF 130 00:06:12,800 --> 00:06:14,520 HIS EARLY BOOKS CALLED LIFE 131 00:06:14,520 --> 00:06:16,920 ASCENDING. HE RECEIVED A 132 00:06:16,920 --> 00:06:21,000 BIOCHEMICAL SOCIETY AWARD AND IN 133 00:06:21,000 --> 00:06:23,880 2016 THE ROYAL SOCIETY MICHAEL 134 00:06:23,880 --> 00:06:25,440 (INAUDIBLE) PRIZE FOR SCIENTIFIC 135 00:06:25,440 --> 00:06:29,440 WRITING. HE IS A FELLOW OF THE 136 00:06:29,440 --> 00:06:30,440 (INAUDIBLE) SOCIETY THE ROLE 137 00:06:30,440 --> 00:06:32,960 SOCIETY OF BIOLOGY, THE 138 00:06:32,960 --> 00:06:34,760 BIOCHEMICAL SOCIETY AND WE ARE 139 00:06:34,760 --> 00:06:38,240 EXTREMELY GRATEFUL TO HIM FOR 140 00:06:38,240 --> 00:06:41,760 COMING TO VISIT NIH FOR THE 141 00:06:41,760 --> 00:06:44,080 FIRST TIME. WHICH WE HOPE WILL 142 00:06:44,080 --> 00:06:45,960 BE PERHAPS NOT JUST THE FIRST 143 00:06:45,960 --> 00:06:47,960 TIME BUT ONE OF MANY YET TO 144 00:06:47,960 --> 00:06:50,880 COME. SO NICK WELCOME TO THE 145 00:06:50,880 --> 00:06:53,560 NIH. AND THE TOPIC OF HIS TALK 146 00:06:53,560 --> 00:06:57,680 IS THE ORIGIN OF CELLS AND GENES 147 00:06:57,680 --> 00:07:00,080 AND WHY IT MATTERS TO MEDICINE. 148 00:07:00,080 --> 00:07:07,000 [APPLAUSE] 149 00:07:07,000 --> 00:07:08,120 >> THANK YOU VERY MUCH FOR THAT 150 00:07:08,120 --> 00:07:09,320 EXTREMELY GENEROUS AND KIND 151 00:07:09,320 --> 00:07:10,920 INTRODUCTION. THANK YOU ALL FOR 152 00:07:10,920 --> 00:07:16,400 BEING HERE. IT FEELS 153 00:07:16,400 --> 00:07:17,800 PRESUMPTIONS TO SAY THE LEAST TO 154 00:07:17,800 --> 00:07:18,880 COME TO NIH AND TALK ABOUT IN 155 00:07:18,880 --> 00:07:20,440 THIS RELATED TO MEDICINE SO I 156 00:07:20,440 --> 00:07:25,280 WILL TELL YOU ORIGIN OF LIFE 157 00:07:25,280 --> 00:07:26,640 INSTEAD BECAUSE MAYBE I CAN TELL 158 00:07:26,640 --> 00:07:28,320 YOU SOMETHING YOU DON'T KNOW. 159 00:07:28,320 --> 00:07:29,400 BUT I DON'T WANT TO BORE YOU TO 160 00:07:29,400 --> 00:07:32,360 TEARS EITHER, FOR THE LAST HALF 161 00:07:32,360 --> 00:07:33,640 OF THE TALK OR THIRD OF THE TALK 162 00:07:33,640 --> 00:07:37,400 I WILL TRY TO PUT TOGETHER WHY 163 00:07:37,400 --> 00:07:39,040 ACTUALLY MATTER AND SEEM AS 164 00:07:39,040 --> 00:07:40,560 STRETCH TO CONNECT THE ORIGIN OF 165 00:07:40,560 --> 00:07:43,240 LIFE WITH MEDICINE TODAY. BUT 166 00:07:43,240 --> 00:07:44,440 THERE ARE GROUNDS FOR DOING SO, 167 00:07:44,440 --> 00:07:47,080 I HOPE WHAT I CAN DO IS NOT TO 168 00:07:47,080 --> 00:07:48,800 TELL YOU THINGS THAT YOU DON'T 169 00:07:48,800 --> 00:07:51,160 KNOW SO MUCH AS PERHAPS GET YOU 170 00:07:51,160 --> 00:07:53,240 TO SEE THINGS YOU DO ALREADY 171 00:07:53,240 --> 00:07:54,520 KNOW ABOUT IN A SLIGHTLY 172 00:07:54,520 --> 00:07:55,560 DIFFERENT WAY SO THAT IS WHAT I 173 00:07:55,560 --> 00:07:59,960 HOPE TO DO TODAY. SO THE ORIGIN 174 00:07:59,960 --> 00:08:01,520 OF LIFE, I'LL VULNERABLE 175 00:08:01,520 --> 00:08:05,480 IMMEDIATELY TO A CHARGE OF 176 00:08:05,480 --> 00:08:07,040 MAKING IT ALL UP. HOW CAN WE 177 00:08:07,040 --> 00:08:09,360 POSSIBLY KNOW? THE ANSWER, WE 178 00:08:09,360 --> 00:08:11,040 CAN'T POSSIBLY KNOW, WE'LL NEVER 179 00:08:11,040 --> 00:08:14,040 KNOW. EASY TO SAY IF WE INVENTED 180 00:08:14,040 --> 00:08:17,240 A TIME MACHINE WE CAN GO BACK 4 181 00:08:17,240 --> 00:08:19,040 BILLION YEARS TO ORIGIN OF LIFE 182 00:08:19,040 --> 00:08:20,600 THEN WE CAN KNOW BUT IT IS A 183 00:08:20,600 --> 00:08:22,680 HISTORICAL QUESTION. NO, I DON'T 184 00:08:22,680 --> 00:08:24,160 THINK SO BECAUSE IF WE INVENT A 185 00:08:24,160 --> 00:08:27,120 TIME MACHINE BACK TO 4 BILLION 186 00:08:27,120 --> 00:08:28,800 YEARS THIS IS ONLY 3 AND A HALF 187 00:08:28,800 --> 00:08:30,280 BILLION YEARS WHAT WOULD WE LOOK 188 00:08:30,280 --> 00:08:32,720 FOR? IF WE FIND IT HOW WOULD WOE 189 00:08:32,720 --> 00:08:35,680 KNOW? SO THESE I'M SURE YOU KNOW 190 00:08:35,680 --> 00:08:42,120 ARE STROMATOLITESS. LIVING 191 00:08:42,120 --> 00:08:44,320 SYSTEMS THOUGH THEY LOOK LIKE 192 00:08:44,320 --> 00:08:47,840 ROCKS, MOST PEOPLE NOT FOUNDED 193 00:08:47,840 --> 00:08:49,360 IN PALEONTOLOGY WOULD UNDERSTAND 194 00:08:49,360 --> 00:08:51,360 THAT IS A LIVING SYSTEM AND IF 195 00:08:51,360 --> 00:08:53,360 WE FIND SOME GREEN SLIME 196 00:08:53,360 --> 00:08:54,720 SOMEWHERE NOT OBVIOUSLY CELLULAR 197 00:08:54,720 --> 00:08:56,320 WOULD THAT BE A STEPPINGSTONE ON 198 00:08:56,320 --> 00:08:58,960 ROOT TO LIFE OR WOULD IT BE A 199 00:08:58,960 --> 00:09:01,720 NON-LIVING -- WHAT WOULD IT BE? 200 00:09:01,720 --> 00:09:03,280 THE ANSWER IS WE HAVE NO IDEA. 201 00:09:03,280 --> 00:09:05,160 THE ONLY WAY WE COULD FIGURE IT 202 00:09:05,160 --> 00:09:08,480 OUT AT ALL IS BY AN INTELLECTUAL 203 00:09:08,480 --> 00:09:09,720 FRAMEWORK WHICH TELL US WHAT WE 204 00:09:09,720 --> 00:09:11,040 ARE ACTUALLY LOOKING FOR. A 205 00:09:11,040 --> 00:09:14,880 FRAMEWORK WHICH SAYS HOW CAN A 206 00:09:14,880 --> 00:09:17,880 STERILE INORGANIC WET ROCKK 207 00:09:17,880 --> 00:09:19,440 PLANET GIVE RISE TO LIFE? HOW 208 00:09:19,440 --> 00:09:21,960 CAN WE GO FROM ONE PLACE TO 209 00:09:21,960 --> 00:09:24,840 LIVING WORLD THAT WE KNOW? AND 210 00:09:24,840 --> 00:09:28,280 THAT, SO MANY IDEAS ON HOW THIS 211 00:09:28,280 --> 00:09:29,960 HAPPENS. MOST OF THEM ARE WRONG. 212 00:09:29,960 --> 00:09:32,600 LET'S FACE IT WE ARE MOSTLY 213 00:09:32,600 --> 00:09:33,840 WRONG ABOUT MOST STUFF. A LOT 214 00:09:33,840 --> 00:09:35,240 HAS CHANGED IN THE LAST FEW 215 00:09:35,240 --> 00:09:36,960 YEARS. I'M NOT TELLING YOU WE 216 00:09:36,960 --> 00:09:38,760 ARE RIGHT ALL OF A SUDDEN BUT 217 00:09:38,760 --> 00:09:41,160 WHAT WE HAVE BEEN DOING, NOT 218 00:09:41,160 --> 00:09:43,480 JUST US, PLENTY OF PEOPLE IS 219 00:09:43,480 --> 00:09:45,200 THINKING ABOUT LIFE AS A GUIDE 220 00:09:45,200 --> 00:09:48,680 TO ITS OWN ORIGIN. YOU SEE 221 00:09:48,680 --> 00:09:51,560 TURTLES ALL THE WAY DOWN. CAN 222 00:09:51,560 --> 00:09:53,960 WE, SEEMS CIRCULAR. CAN E USE 223 00:09:53,960 --> 00:09:55,400 LIFE AS A GUIDE TO ITS OWN 224 00:09:55,400 --> 00:09:55,640 ORIGIN? 225 00:09:55,640 --> 00:09:57,680 I THINK WE CAN. I WILL SHOW YOU 226 00:09:57,680 --> 00:09:59,320 WHY. THIS IS IN THREE WAYS I 227 00:09:59,320 --> 00:10:03,400 WILL TALK ABOUT. ENERGY, THE WAY 228 00:10:03,400 --> 00:10:06,480 CELLS POWER WORK, IS NOT HOW YOU 229 00:10:06,480 --> 00:10:08,400 MIGHT IMAGINE, IT IS NOT JUST 230 00:10:08,400 --> 00:10:10,760 ABOUT ATP NOT JUST CHEMISTRY IN 231 00:10:10,760 --> 00:10:12,920 A BUCK, IT IS ABOUT ELECTRIC 232 00:10:12,920 --> 00:10:15,280 MEMBRANES POWER WORK SO HOW DID 233 00:10:15,280 --> 00:10:18,480 THAT COME TO BE? SECOND, 234 00:10:18,480 --> 00:10:20,040 METABOLISM, WE THINK IN COMPLEX 235 00:10:20,040 --> 00:10:22,240 MEDICAL SYSTEMS OF ALL KINDS OF 236 00:10:22,240 --> 00:10:24,840 DIFFERENT ASPECTS OF METABOLISM 237 00:10:24,840 --> 00:10:26,800 BUT THERE IS A SMALL CORE SHED 238 00:10:26,800 --> 00:10:29,120 BY LIFE ON EFFORT INCLUDING 239 00:10:29,120 --> 00:10:30,400 BACTERIA AND EARLIEST FORMS OF 240 00:10:30,400 --> 00:10:32,080 LIFE. THERE IS COMMONALITY TO 241 00:10:32,080 --> 00:10:34,120 THAT SO THIS UNIVERSAL CORE IS 242 00:10:34,120 --> 00:10:37,760 TELLING US SOMETHING ABOUT THE 243 00:10:37,760 --> 00:10:39,120 CONDITIONS UNDER WHICH LIFE 244 00:10:39,120 --> 00:10:41,560 MIGHT HAVE STARTED. GENES, 245 00:10:41,560 --> 00:10:42,560 GENETIC INFORMATION. WHERE DOES 246 00:10:42,560 --> 00:10:44,400 THAT COME FROM? BUN ONE OF THE 247 00:10:44,400 --> 00:10:45,560 BIGGEST QUESTIONS IN BIOLOGY. 248 00:10:45,560 --> 00:10:49,240 THERE'S PATTERNS IN THE GENETIC 249 00:10:49,240 --> 00:10:50,800 CODE REINTERPRETED NOW WHICH WE 250 00:10:50,800 --> 00:10:52,160 HAVE KNOWN FOR DECADES WHICH 251 00:10:52,160 --> 00:10:54,360 ARELINGING BINGING TO POINT TO A 252 00:10:54,360 --> 00:10:55,400 -- BEGINNING TO POINT TO A 253 00:10:55,400 --> 00:10:56,840 POSSIBLE ANSWER. THIS IS ALL 254 00:10:56,840 --> 00:10:59,000 VERY EXCITING STUFF. IT MIGHT BE 255 00:10:59,000 --> 00:11:01,040 WRONG BUT IT MIGHT BE RIGHT AND 256 00:11:01,040 --> 00:11:02,400 FUN TO THINK ABOUT AND FUN TO 257 00:11:02,400 --> 00:11:03,760 COME HERE TO TELL YOU ABOUT IT 258 00:11:03,760 --> 00:11:05,640 SO QUICKLY, LIFE IS ELECTRIC. 259 00:11:05,640 --> 00:11:07,560 JUST TO GET USED TO MY DIAGRAMS 260 00:11:07,560 --> 00:11:10,280 BECAUSE YOU CAN SEE IMMEDIATELY 261 00:11:10,280 --> 00:11:12,080 I'M NOT GOOD AT POWERPOINT. 262 00:11:12,080 --> 00:11:13,080 KREBS CYCLE RIGHT IN THE MIDDLE 263 00:11:13,080 --> 00:11:16,760 THERE. NOT GOING TO GO INTO VERY 264 00:11:16,760 --> 00:11:20,320 MANY DETAILS BUT YOU WILL KNOW 265 00:11:20,320 --> 00:11:23,840 THE WORLD -- WE ARE STRIPPING 266 00:11:23,840 --> 00:11:26,360 GLUCOSE DOWN. SOMETHING HAS GONE 267 00:11:26,360 --> 00:11:29,240 WRONG. STRIPPING GLUCOSE NOW TO 268 00:11:29,240 --> 00:11:30,920 ACETYLC, OA FEEDING TO THE KREBS 269 00:11:30,920 --> 00:11:32,440 CYCLE. ALL I WANT YOU TO TAKE 270 00:11:32,440 --> 00:11:34,680 NOTE IS PULLING OUT HYDROGEN, 271 00:11:34,680 --> 00:11:37,560 NOT AS THE GASES NEDH BUT JUST 272 00:11:37,560 --> 00:11:39,880 PUT THE TERMINOLOGY TO ONE SIDE. 273 00:11:39,880 --> 00:11:41,560 HYDROGEN ATOMS COMING OUT OF THE 274 00:11:41,560 --> 00:11:43,760 KREBS CYCLE. THEY ARE BEING FED 275 00:11:43,760 --> 00:11:46,720 TO OXYGEN, NO AS HYDROGEN ATOM 276 00:11:46,720 --> 00:11:49,480 BUS ELECTRONS AND PROTONS WHICH 277 00:11:49,480 --> 00:11:51,360 POLYSEPARATE PATHS SO CO 2 AND 278 00:11:51,360 --> 00:11:52,520 HYDROGEN ARE COMING OUT OF THE 279 00:11:52,520 --> 00:11:54,760 KREBS CYCLE, THAT IS A KEY THING 280 00:11:54,760 --> 00:11:58,960 TO KEEP IN MIND. THE CURRENT OF 281 00:11:58,960 --> 00:12:00,400 ELECTRONS FLOWING THROUGH 282 00:12:00,400 --> 00:12:02,080 OXYGEN, IT THE USN'T HAVE TO BE 283 00:12:02,080 --> 00:12:03,840 OXYGEN, IT COULD BE NITRATE OR 284 00:12:03,840 --> 00:12:05,520 NITRITE OR ANY NUMBER OF 285 00:12:05,520 --> 00:12:08,880 DIFFERENT INORGANIC MOLECULES. 286 00:12:08,880 --> 00:12:11,680 THE CURRENT OF ELECTRONS FLOWING 287 00:12:11,680 --> 00:12:13,760 TO LEK ELECTRONIC ACCEPTOR 288 00:12:13,760 --> 00:12:17,120 POWERS THE EXTRUSION OF IONS, IT 289 00:12:17,120 --> 00:12:19,920 CAN BE SODIUM IONS AND OTHERS 290 00:12:19,920 --> 00:12:22,840 BUT NORMALLY PROTONS. THIS IDEA 291 00:12:22,840 --> 00:12:25,120 GOES BACK TO PREFER MITCHELL IN 292 00:12:25,120 --> 00:12:28,000 THE 1960s. THIS PROBABLY LOOKS 293 00:12:28,000 --> 00:12:29,240 THE SAME. IT IS DIFFERENT IN ONE 294 00:12:29,240 --> 00:12:31,680 KEY WAY, THOSE ARROWS MANY ON 295 00:12:31,680 --> 00:12:33,640 THE KREBS CYCLE ARE INVERTED 296 00:12:33,640 --> 00:12:34,800 THEIR DIRECTION. THEY ARE NOW 297 00:12:34,800 --> 00:12:36,480 GOING OPPOSITE DIRECTION AND WE 298 00:12:36,480 --> 00:12:38,800 HAVE HYDROGEN BEING SUCKED IN 299 00:12:38,800 --> 00:12:41,920 AND CO 2 BEING SUCKED IN. THIS 300 00:12:41,920 --> 00:12:43,520 IS THE REVERSE KREBS CYCLE, 301 00:12:43,520 --> 00:12:45,640 PLENTY OF BACTERIA LIVING IN 302 00:12:45,640 --> 00:12:49,120 HYDRO THERMAL SYSTEMS AND 303 00:12:49,120 --> 00:12:50,800 GEOTHERMAL SYSTEMS AND STAGNANT 304 00:12:50,800 --> 00:12:54,560 MUGS AND ALL PLACES THAT HAVE A 305 00:12:54,560 --> 00:12:56,280 REVERSE KREBS CYCLE, IT 306 00:12:56,280 --> 00:12:58,200 SURPRISES ME THAT IS NOT COMMON 307 00:12:58,200 --> 00:12:59,960 KNOWLEDGE IN THE BIOCHEMISTRY 308 00:12:59,960 --> 00:13:02,040 TEXTBOOKS MORE MEDICALLY 309 00:13:02,040 --> 00:13:04,480 INCLINED TEXTBOOKS IT TENDS TO 310 00:13:04,480 --> 00:13:06,160 MENTION EXISTENCE, I KNEW 311 00:13:06,160 --> 00:13:07,200 NOTHING ABOUT IT UNTIL YEARS 312 00:13:07,200 --> 00:13:10,240 AFTER MY DEGREE IN BIOCHEMISTRY. 313 00:13:10,240 --> 00:13:11,360 THEY ARE DOING EXACTLY THE 314 00:13:11,360 --> 00:13:13,120 OPPOSITE. THEY ARE SUCKING IN 315 00:13:13,120 --> 00:13:15,240 HYDROGEN CO 2 REACTING THEM 316 00:13:15,240 --> 00:13:17,040 TOGETHER TO FORM KREBS CYCLE 317 00:13:17,040 --> 00:13:18,080 INTERMEDIATES. IT IS LONGER 318 00:13:18,080 --> 00:13:20,280 THAN THE KREBS CYCLE AND 319 00:13:20,280 --> 00:13:24,640 INCLUDES ACETYLCOA AND PYRUVATE 320 00:13:24,640 --> 00:13:26,920 AND PHOSPHOTEAL PYRUVATE AS 321 00:13:26,920 --> 00:13:29,400 WELL. SO ENENCOMPASSING AND IT 322 00:13:29,400 --> 00:13:32,080 IS ABOUT THE CORE OF 323 00:13:32,080 --> 00:13:33,960 BIOCHEMISTRY. SO SLIGHTRY 324 00:13:33,960 --> 00:13:37,200 UNSTABLE ME DOING SOMETHING OR 325 00:13:37,200 --> 00:13:40,640 WHAT. FROM ACIDS IN THE KREBS 326 00:13:40,640 --> 00:13:45,240 CYCLE WE ARE MAKING AMINO ACIDS, 327 00:13:45,240 --> 00:13:46,760 SUGARS LIPIDS, HS THE HEART OF 328 00:13:46,760 --> 00:13:49,280 ANN BOLLIC METABOLISM, AND IT IS 329 00:13:49,280 --> 00:13:51,360 LESS OBVIOUS WITHIN MEDICINE 330 00:13:51,360 --> 00:13:52,720 BECAUSE WE SEE THE KREBS CYCLE 331 00:13:52,720 --> 00:13:54,840 AS THE OXIDATIVE KREBS CYCLE 332 00:13:54,840 --> 00:13:57,040 WITHIN CELLS, CYTOPLASM IS 333 00:13:57,040 --> 00:13:59,280 DIFFERENT, PYRUVATE AND 334 00:13:59,280 --> 00:14:00,360 GLYCOLYSIS ARE OUTSIDE THE SIGH 335 00:14:00,360 --> 00:14:03,320 SOL SO IT IS NOT OBVIOUS -- 336 00:14:03,320 --> 00:14:04,880 CYTOSOL SO NOT OBVIOUS THIS IS 337 00:14:04,880 --> 00:14:06,960 THE HEART OF ANN BOLLIC 338 00:14:06,960 --> 00:14:08,120 METABOLISM BUT STEP BACK TO 339 00:14:08,120 --> 00:14:10,560 THINK ABOUT THE BACTERIA THAT IS 340 00:14:10,560 --> 00:14:11,880 WHAT IT IS. SO THE THIRD THING, 341 00:14:11,880 --> 00:14:15,120 THIS IS JUST A TASTE OF ARGUMENT 342 00:14:15,120 --> 00:14:17,800 LATER ON, THESE PATTERNS IN THE 343 00:14:17,800 --> 00:14:18,920 GENETIC CODE THAT HAVE BEEN 344 00:14:18,920 --> 00:14:21,920 KNOWN ABOUT REALLY SINCE THE 345 00:14:21,920 --> 00:14:23,480 1960s, CARL WOES IN THE 346 00:14:23,480 --> 00:14:26,000 1960s POINTING THIS OUT IN 347 00:14:26,000 --> 00:14:30,520 1965, 1966 PAPERS IN PNAS. THERE 348 00:14:30,520 --> 00:14:33,280 ARE EFFECTIVELY SEVERAL PATTERNS 349 00:14:33,280 --> 00:14:34,440 THAT SUGGEST THAT THE 350 00:14:34,440 --> 00:14:35,520 RELATIONSHIP WITH METABOLISM 351 00:14:35,520 --> 00:14:38,400 WITH THE PRECURSOR OF THE AMINO 352 00:14:38,400 --> 00:14:42,000 ACID BUT ALSO WITH THE HYDRO FOR 353 00:14:42,000 --> 00:14:44,280 BUSINESSTY OF THE AMINO AND SIZE 354 00:14:44,280 --> 00:14:47,160 OF AMINO ACID. I'M SUGGESTING 355 00:14:47,160 --> 00:14:48,680 SYSTEM -- AM I STEPPING ON A 356 00:14:48,680 --> 00:14:54,640 POWER CABLE SOMEWHERE? WHICH 357 00:14:54,640 --> 00:14:56,080 MEANS ALL I WANT TO GO I A CROSS 358 00:14:56,080 --> 00:14:57,520 IN THIS MOMENT IS IF YOU HAVE A 359 00:14:57,520 --> 00:15:00,560 COMPLETELY RANDOM PIECE OF RNA 360 00:15:00,560 --> 00:15:01,760 AN YOU HAVE SOME KIND OF 361 00:15:01,760 --> 00:15:04,440 PHYSICAL TEMPLATING HYDRO FOLKIC 362 00:15:04,440 --> 00:15:06,880 BASE WILL INTERACT WITH 363 00:15:06,880 --> 00:15:08,720 HYDROPHOBIC AMINO ACID AND IF 364 00:15:08,720 --> 00:15:11,080 THAT POLYMERIZES YOU HAVE A 365 00:15:11,080 --> 00:15:14,680 POLYMERIC PEPTIDE WHICH IS 366 00:15:14,680 --> 00:15:16,400 TEMPLATED BY THE RNA IN SOME WAY 367 00:15:16,400 --> 00:15:19,160 SO RANDOM RNA WILL GIVE RISE TO 368 00:15:19,160 --> 00:15:21,560 NON-RANDOM PEPTIDE THAT HAS 369 00:15:21,560 --> 00:15:22,240 FUNCTION DEPENDING ON THE 370 00:15:22,240 --> 00:15:25,240 SETTING. SO THE ORIGIN OF 371 00:15:25,240 --> 00:15:26,440 INFORMATION IN BIOLOGY IS VERY, 372 00:15:26,440 --> 00:15:28,040 VERY CONTEXT IN SETTING 373 00:15:28,040 --> 00:15:29,440 DEPENDENT AND I WILL SUGGEST TO 374 00:15:29,440 --> 00:15:32,240 YOU HOW THAT COMES ABOUT. 375 00:15:32,240 --> 00:15:33,040 ANOTHER INTERESTING POINT ABOUT 376 00:15:33,040 --> 00:15:35,040 THIS. WHAT I'M SAYING HERE IS 377 00:15:35,040 --> 00:15:37,360 THAT EFFECTIVELY ELECTRICITY ONE 378 00:15:37,360 --> 00:15:40,760 FORM OR ANOTHER IS DRIVING 379 00:15:40,760 --> 00:15:43,120 METABOLISM CORE ANN BOLLIC 380 00:15:43,120 --> 00:15:44,440 METABOLISM GIVING TO GENES AND 381 00:15:44,440 --> 00:15:45,560 IS ALL HAPPENING IN THE SAME 382 00:15:45,560 --> 00:15:47,760 PLACE. IT IS NOT AS IF YOU MAKE 383 00:15:47,760 --> 00:15:49,560 GENES OVER THERE AND YOU MAKE 384 00:15:49,560 --> 00:15:51,000 SOMETHING ELSE OVER HERE AND 385 00:15:51,000 --> 00:15:55,800 THEY COME TOGETHER SOMEHOW. TO 386 00:15:55,800 --> 00:15:59,000 HAVE ANION GRADIENT ACROSS 387 00:15:59,000 --> 00:16:00,840 MEMBRANE DRIVING METABOLISM, 388 00:16:00,840 --> 00:16:01,920 THEY HAVE TO BE NEXT TO ETCH OOH 389 00:16:01,920 --> 00:16:03,160 OTHER SAME PLACE SAME TIME AND 390 00:16:03,160 --> 00:16:04,080 IF GENES RESEARCH MANYING THEY 391 00:16:04,080 --> 00:16:05,440 HAVE TO EMERGE IN THE SAME 392 00:16:05,440 --> 00:16:07,360 ENVIRONMENT AT THE SAME PLACE 393 00:16:07,360 --> 00:16:09,080 SAME TIME, GREAT TO DO LAB WORK 394 00:16:09,080 --> 00:16:10,320 ON THESE THINGS BECAUSE WE CAN 395 00:16:10,320 --> 00:16:14,320 DO IT SAME PLACE SAME TIME. IT 396 00:16:14,320 --> 00:16:16,600 IS NOT THE PREDOMINANT IDEA IN 397 00:16:16,600 --> 00:16:17,800 THE FIELD I WOULD SAY. YOU 398 00:16:17,800 --> 00:16:19,200 SHOULD BE -- I HAVE TO WARN YOU 399 00:16:19,200 --> 00:16:23,760 UP FRONT THIS IS LIGHTLY 400 00:16:23,760 --> 00:16:27,760 HIERATICAL. I SAID REALLY? IT IS 401 00:16:27,760 --> 00:16:30,160 ACTUALLY FEASIBLE BELIEVABLE? 402 00:16:30,160 --> 00:16:33,640 RATIONALE OR RANNABLE TO SAY -- 403 00:16:33,640 --> 00:16:35,800 RASHABLE TO SAY THESE THINGS CAN 404 00:16:35,800 --> 00:16:37,480 TAKE PLACE SAME TIME SAME PLACE? 405 00:16:37,480 --> 00:16:39,280 I HAVE TO ADMIT A POINT. I KIND 406 00:16:39,280 --> 00:16:41,800 OF AGREE WITH YOU IT DOESN'T 407 00:16:41,800 --> 00:16:42,920 SEEM PLAUSIBLE, DOES IT? THERE 408 00:16:42,920 --> 00:16:45,920 IS A PLACE, NOT WEDDED TO THIS 409 00:16:45,920 --> 00:16:47,720 AS A PLACE FOR THE ORIGIN OF 410 00:16:47,720 --> 00:16:49,080 LIFE BUT IT WORKS WELL AND THERE 411 00:16:49,080 --> 00:16:50,920 MIGHT BE OR SETSINGS EQUIVALENT 412 00:16:50,920 --> 00:16:53,040 TO THIS. -- SETTINGS EQUIVALENT. 413 00:16:53,040 --> 00:16:54,800 THIS WAS DISCOVERED BY DEB KELLY 414 00:16:54,800 --> 00:16:58,000 ON THE ALVIN SUBMERSIBLE IN THE 415 00:16:58,000 --> 00:17:00,720 YEAR 2000. THIS IS LOST FITTING 416 00:17:00,720 --> 00:17:03,400 WHICH IS A HYDRO THERMAL VENT 417 00:17:03,400 --> 00:17:05,520 SYSTEM OFF AXIS OF THE MID 418 00:17:05,520 --> 00:17:06,840 ATLANTIC RIDGE 15 MILES AFTER 419 00:17:06,840 --> 00:17:08,560 AXIS. AND IT IS NOT LIKE THE 420 00:17:08,560 --> 00:17:09,960 BLACK SMOKE EVENTS MOST OF US 421 00:17:09,960 --> 00:17:11,960 ARE FAMILIAR WITH. IT IS NO 422 00:17:11,960 --> 00:17:14,880 SMOKE COMING OUT OF IT AT ALL, 423 00:17:14,880 --> 00:17:16,880 THEY LOOK ALMOST INACTIVE BUT 424 00:17:16,880 --> 00:17:19,160 THESE ARE ACTIVE VENTING 425 00:17:19,160 --> 00:17:21,320 SYSTEMS. AND SHE IS HOLDING IN 426 00:17:21,320 --> 00:17:23,480 HER LEFT HAND A LUNCH OF BLACK 427 00:17:23,480 --> 00:17:25,680 SMOKE WHICH LOOKS ACHE A CAN 428 00:17:25,680 --> 00:17:27,360 IMNY THE WAY SMOKE COMES OUT. 429 00:17:27,360 --> 00:17:29,600 IN HER RIGHT HAND SHE IS HOLDING 430 00:17:29,600 --> 00:17:32,760 A PIECE OF LOST CITY, IT LOOKS 431 00:17:32,760 --> 00:17:44,440 LIKE POUR OUT POWER OUTSID POURS 432 00:17:47,960 --> 00:17:50,840 WAS THIS PICTURE OF HIM PHOTO 433 00:17:50,840 --> 00:17:53,160 SHOPPED UP WAS IN A NATURE 434 00:17:53,160 --> 00:17:56,480 FEATURE IN 2009 UNBELIEVE BY 435 00:17:56,480 --> 00:18:03,400 THEY DRESSED HIM UP AS A 436 00:18:03,400 --> 00:18:05,000 RENAISSANCE MAN, THEY DRESSED 437 00:18:05,000 --> 00:18:06,400 HIM UP AS BIRTH OF LIFE, AND 438 00:18:06,400 --> 00:18:08,720 THEY GOT A LITTLE BIT OF 439 00:18:08,720 --> 00:18:10,040 REACTOR, HE WAS IN JET 440 00:18:10,040 --> 00:18:11,760 PROPULSION SO BIT OF HIS REACTOR 441 00:18:11,760 --> 00:18:13,800 THERE, THIS IS A SECTION OF LOSS 442 00:18:13,800 --> 00:18:15,680 CITY SHOWI SHOWING THE MINERALID 443 00:18:15,680 --> 00:18:16,800 SPONGE STRUCTURE. THE KEY POINT 444 00:18:16,800 --> 00:18:19,280 HE DESCRIBED THESE SYSTEMS AS 445 00:18:19,280 --> 00:18:21,280 EFFECTIVELY ELECTROCHEMICAL FLOW 446 00:18:21,280 --> 00:18:23,280 REACTORS YOU HAVE FLUIDS WINDING 447 00:18:23,280 --> 00:18:27,120 THROUGH -- ALKALINE HYDRO 448 00:18:27,120 --> 00:18:29,680 THERMAL FLUID COMING,K AING OUT 449 00:18:29,680 --> 00:18:31,960 OF OCEAN WATER, THE WATERS WERE 450 00:18:31,960 --> 00:18:33,360 PROBABLY ACIDIC SO THEY WOULD 451 00:18:33,360 --> 00:18:34,960 HAVE BEEN MIXING WITHIN THOSE 452 00:18:34,960 --> 00:18:36,960 SYSTESYSTEMS. NO OXYGEN. THE ABE 453 00:18:36,960 --> 00:18:39,800 OF OXYGEN MEANS PLENTY OF 454 00:18:39,800 --> 00:18:41,400 DISSOLVED IRON AND OTHER 455 00:18:41,400 --> 00:18:43,240 TRANSITION METALS NICKEL AND 456 00:18:43,240 --> 00:18:44,840 THINGS LIKE THAT SO CATALYTIC 457 00:18:44,840 --> 00:18:49,480 WALLS NOT JUST ION SUR FEED BUT 458 00:18:49,480 --> 00:18:50,280 INCLUDING IRON SKULL VIED. THE 459 00:18:50,280 --> 00:18:52,320 OTHER IS THE FLUIDS ARE 460 00:18:52,320 --> 00:18:54,720 ALKALINE. HYDRO HER MALL FLUIDS 461 00:18:54,720 --> 00:18:57,520 ARE WITHOUT PH 11 WHICH SHOULD 462 00:18:57,520 --> 00:19:00,120 UNDERSTAND EXTREME AND THEY ARE 463 00:19:00,120 --> 00:19:01,280 BUBBLING WITH HIGH ROW GENERAL 464 00:19:01,280 --> 00:19:04,360 GAS SO THEY -- HYDROGEN GAS. SO 465 00:19:04,360 --> 00:19:07,240 THEY ARE HYDROGENATED -- NOT 466 00:19:07,240 --> 00:19:08,440 SURE YOU WANT TO DRINK IT AND 467 00:19:08,440 --> 00:19:09,200 THE OCEAN I MENTION REDIRECT 468 00:19:09,200 --> 00:19:11,320 EXAMINATION ACIDIC. SO WE HAVE 469 00:19:11,320 --> 00:19:12,920 PH GRADIENTS ACROSS THE 470 00:19:12,920 --> 00:19:19,240 BARRIERS. PH GRADIANS IS SEVEN 471 00:19:19,240 --> 00:19:20,320 ORDERS OF MEMBER TUESDAY 472 00:19:20,320 --> 00:19:22,280 DIFFERENT IN PROTONE STRUCTU ST. 473 00:19:22,280 --> 00:19:24,480 IT IS SAY IT IS A NATURAL 474 00:19:24,480 --> 00:19:25,760 PROTONE MOTOR FORCE AND THAT IS 475 00:19:25,760 --> 00:19:27,680 WHERE I'M GOING WITH THIS. HERE 476 00:19:27,680 --> 00:19:30,320 IS HYPOTHESIS. BE INTERESTING TO 477 00:19:30,320 --> 00:19:31,640 KNOW WHAT YOU MAKE OF THIS BY 478 00:19:31,640 --> 00:19:33,560 THE END OF THE LECTURE BUT WE 479 00:19:33,560 --> 00:19:34,920 START WITH THINK OF GRAY AS THE 480 00:19:34,920 --> 00:19:36,720 PORE IN ONE OF THESE HYDRO 481 00:19:36,720 --> 00:19:42,360 THERMAL VENTSS. WE HAVE HYDROGEN 482 00:19:42,360 --> 00:19:44,360 IONS OUTSIDE, FLUIDS INSIDE, WE 483 00:19:44,360 --> 00:19:45,440 HAVE PROTONS CROSSING THE 484 00:19:45,440 --> 00:19:47,800 BARRIER, NOT SURE WHAT IS GOING 485 00:19:47,800 --> 00:19:50,000 ON THERE. EFFECTIVELY DRIVING 486 00:19:50,000 --> 00:19:51,240 REACTION BETWEEN HYDROGEN AN CO 487 00:19:51,240 --> 00:19:53,360 2 LOWERING KINETIC BARRIER TO 488 00:19:53,360 --> 00:19:54,600 THAT REACTION HAPPENING AND 489 00:19:54,600 --> 00:19:57,880 DRIVING THE REACTION TO MAKE C 490 00:19:57,880 --> 00:20:01,320 CYCLE INTERMEDIATES AND AMINO 491 00:20:01,320 --> 00:20:02,560 ACIDS AND LIPIDS IN THAT SYSTEM. 492 00:20:02,560 --> 00:20:04,480 IF WE ARE MAKING LIBBEDS WE 493 00:20:04,480 --> 00:20:06,600 EXPECT TO FORM A BIOLAYER 494 00:20:06,600 --> 00:20:09,200 MEMBRANE THAT WILL PLATE ITSELF, 495 00:20:09,200 --> 00:20:11,640 SHOWING YOUR HERE BECAUSE IT 496 00:20:11,640 --> 00:20:13,840 LOOKS NICE THAT WAY. SO WE HAVE 497 00:20:13,840 --> 00:20:16,640 A PROTO CELL INSIDE THE HYDRO 498 00:20:16,640 --> 00:20:18,000 THERMAL CORE. NOW WE HAVE A 499 00:20:18,000 --> 00:20:20,000 PARTIALLY CLOSED SYSTEM, THE 500 00:20:20,000 --> 00:20:21,440 CONCENTRATION IS A BIT HIGHER 501 00:20:21,440 --> 00:20:23,000 MAYBE THE DRIVING FORCE GETS 502 00:20:23,000 --> 00:20:24,640 BETTER SO PERHAPS WE CAN PUSH A 503 00:20:24,640 --> 00:20:25,880 LITTLE BIT FURTHER THROUGH 504 00:20:25,880 --> 00:20:26,920 BIOCHEMISTRY TO MAKE NOT JUST 505 00:20:26,920 --> 00:20:28,840 APPLY KNOW ACIDS AN LIPIDS BUT 506 00:20:28,840 --> 00:20:32,360 SUGARS AND ULTIMATELY 507 00:20:32,360 --> 00:20:33,280 NUCLEOTIDES. YOU ARE THINKING 508 00:20:33,280 --> 00:20:34,840 WHAT A HAND WAVING GUY TELLING 509 00:20:34,840 --> 00:20:36,720 YOU THIS STUFF HOW IS THAT 510 00:20:36,720 --> 00:20:38,040 BELIEVABLE? HOPE TO CHANGE YOUR 511 00:20:38,040 --> 00:20:41,560 MIND OVER THE NEXT TEN MINUTES. 512 00:20:41,560 --> 00:20:43,800 FINALLY IN THE RIGHT HAND SIDE 513 00:20:43,800 --> 00:20:45,720 THERE,S WE HAVE SOME RNA IN THIS 514 00:20:45,720 --> 00:20:47,160 SYSTEM, WE HAVE AN RNA WORLD THE 515 00:20:47,160 --> 00:20:50,080 FIRST POLYMERS INTERACTING WITH 516 00:20:50,080 --> 00:20:51,280 AMINO ASSISTEDS FORMING SHORT 517 00:20:51,280 --> 00:20:52,800 PEPTIDES, EFFECTIVELY A DIRTY 518 00:20:52,800 --> 00:20:56,120 RNA WORLD INSIDE GROWING PROTON 519 00:20:56,120 --> 00:20:59,120 CELLS INSIDE A HYDRO THERMAL 520 00:20:59,120 --> 00:21:00,760 VENT. THE HYPOTHESIS. THE GOOD 521 00:21:00,760 --> 00:21:02,720 THING IS EVERY STEP IS TESTABLE, 522 00:21:02,720 --> 00:21:06,560 AT LEAST IN PRINCIPLE. SO I 523 00:21:06,560 --> 00:21:08,440 WILL TALK ABOUT EACH BIG IDEA IN 524 00:21:08,440 --> 00:21:12,080 TURN BEFORE I COME INTO MY -- 525 00:21:12,080 --> 00:21:15,720 ENERGY FLOW. PETER MITCHELL AND 526 00:21:15,720 --> 00:21:17,160 JENNIFER ARE BEING GOING OUT OF 527 00:21:17,160 --> 00:21:20,720 MY WAY TO DO ACOLYTE TO JENNIFER 528 00:21:20,720 --> 00:21:24,000 BECAUSE WITHOUT HER DO A CALL 529 00:21:24,000 --> 00:21:25,800 OUT, MITCHELL HAD BRILLIANT 530 00:21:25,800 --> 00:21:28,440 IDEAS BUT HE WASLESS IN THE AND 531 00:21:28,440 --> 00:21:30,320 IT WAS JENNIFER WHO DID THE 532 00:21:30,320 --> 00:21:31,440 EXPERIMENTS, IT WASN'T MITCHELL 533 00:21:31,440 --> 00:21:33,600 SAID YOU DO THIS EXPERIMENT OR 534 00:21:33,600 --> 00:21:36,680 THAT ONE, JENNIFER WAS 535 00:21:36,680 --> 00:21:37,960 INTELLECTUALLY SHE WAS COMING UP 536 00:21:37,960 --> 00:21:39,520 WITH THE EXPERIMENTS AND THE ONE 537 00:21:39,520 --> 00:21:41,880 WHO NAILED THE IDEA SO PEOPLE 538 00:21:41,880 --> 00:21:42,480 LIKE (INAUDIBLE) HERE IF THE 539 00:21:42,480 --> 00:21:46,440 U.S. BEGAN TO TAKE IT SERIOUSLY. 540 00:21:46,440 --> 00:21:47,680 I DON'T THINK SHE GOT ANYTHING 541 00:21:47,680 --> 00:21:49,360 LIKE THE CREDIT SHE DESERVES IS. 542 00:21:49,360 --> 00:21:51,600 MITCHELL GOT THE NOBEL PRIZE BY 543 00:21:51,600 --> 00:21:53,800 HIMSELF IN 1978, IT CERTAINLY 544 00:21:53,800 --> 00:21:55,640 WAS A WORLD CHANGING IDEA. IT 545 00:21:55,640 --> 00:21:58,040 WAS A REMARKABLE IDEA AND THE 546 00:21:58,040 --> 00:22:01,160 IDEA WAS MITCHELL'S IDEA BUT THE 547 00:22:01,160 --> 00:22:02,400 DEMONSTRATION WAS IT WAS REAL 548 00:22:02,400 --> 00:22:04,320 SCIENCE WAS COMING FROM 549 00:22:04,320 --> 00:22:05,080 JENNIFER, SHE WAS REMARKABLE 550 00:22:05,080 --> 00:22:09,520 WOMAN. PUTTING THAT ASIDE, HERE 551 00:22:09,520 --> 00:22:11,440 IS A QUOTE FROM MITCHELL, AS A 552 00:22:11,440 --> 00:22:15,880 CONFERENCE IN 1957 IN MOSCOW. ON 553 00:22:15,880 --> 00:22:18,320 THE ORIGIN OF LIFE. HE SAID THIS 554 00:22:18,320 --> 00:22:20,480 WAS FOUR YEARS BEFORE THE 555 00:22:20,480 --> 00:22:22,600 HYPOTHESIS IN NATURE IN 1961. HE 556 00:22:22,600 --> 00:22:24,360 SAID I CANNOT CONSIDER THE 557 00:22:24,360 --> 00:22:25,400 ORGANISM WITHOUT ITS ENVIRONMENT 558 00:22:25,400 --> 00:22:27,480 FROM A FORMAL POINT OF VIEW TWO 559 00:22:27,480 --> 00:22:30,160 MAY BE REGARDED EQUIVALENT 560 00:22:30,160 --> 00:22:31,360 PHASES WHICH DYNAMIC CONTACT IS 561 00:22:31,360 --> 00:22:32,800 MAINTAIND BY THE MEMBRANES THAT 562 00:22:32,800 --> 00:22:34,920 SEPARATE AND LINK THEM. SO WHEN 563 00:22:34,920 --> 00:22:37,440 I SAY WHEN HE SAYS ORGANISM, 564 00:22:37,440 --> 00:22:40,120 THINK BACTERIAL CELL, FORGET 565 00:22:40,120 --> 00:22:41,960 CELL WALL JUST THINK BACTERIAL 566 00:22:41,960 --> 00:22:45,280 WITH CELL MEMBRANE AND IT IS 567 00:22:45,280 --> 00:22:47,040 EQUIVALENT PHASE INSIDE OF THE 568 00:22:47,040 --> 00:22:48,280 CELL AND OUTSIDE ARE E REQUEST 569 00:22:48,280 --> 00:22:49,960 I'VE LENT FADES. STRANGE TO SAY 570 00:22:49,960 --> 00:22:52,960 BUT -- PHASES. -- EQUIVALENT 571 00:22:52,960 --> 00:22:53,520 PHASES. 572 00:22:53,520 --> 00:22:55,800 IF THERE IS A CELL OR ORGANISM 573 00:22:55,800 --> 00:22:57,200 IT IS HELPFUL TO THINK 574 00:22:57,200 --> 00:22:58,440 EQUIVALENT PHASES WITH BARRIER 575 00:22:58,440 --> 00:23:01,080 SEPARATING THEM. IT IS A 576 00:23:01,080 --> 00:23:01,840 PRODUCTIVE WAY OF SEEING THE 577 00:23:01,840 --> 00:23:03,680 QUESTION. A LOT OF WHAT I AM 578 00:23:03,680 --> 00:23:06,600 GOING TO PUT TO YOU NOW THE SEED 579 00:23:06,600 --> 00:23:08,480 REALLY CAME FROM MITCHELL'S 580 00:23:08,480 --> 00:23:11,800 THINKING BACK IN THE 1950s. I 581 00:23:11,800 --> 00:23:13,440 THOUGHT FOR A LONG TIME WHAT IS 582 00:23:13,440 --> 00:23:16,680 IT -- WHAT CAN I DO? IN AN 583 00:23:16,680 --> 00:23:18,760 INORGANIC WORLD WHAT CAN A 584 00:23:18,760 --> 00:23:21,040 Ph.D. GRADIENT ACROSS 585 00:23:21,040 --> 00:23:22,840 INORGANIC BARRIER DO? NOT GOING 586 00:23:22,840 --> 00:23:25,640 TO MAKE ATP. WHAT IT CAN DO IS 587 00:23:25,640 --> 00:23:26,960 DRIVE REACTION BETWEEN 588 00:23:26,960 --> 00:23:28,440 HYDROGENND A CO 2. THIS WAS 589 00:23:28,440 --> 00:23:30,080 PURE SIMPLE PHYSICAL CHEMISTRY. 590 00:23:30,080 --> 00:23:32,280 THIS IS NOT GOING TO GO INTO THE 591 00:23:32,280 --> 00:23:34,560 REDOX POTENTIAL UNLESS YOU ASK 592 00:23:34,560 --> 00:23:37,040 ME SPECIFICALLY AFTERWARD BUT 593 00:23:37,040 --> 00:23:39,360 JUST KNOW UPHILL HYDROGEN WON'T 594 00:23:39,360 --> 00:23:43,240 REACT WITH CO 2 FOR, 595 00:23:43,240 --> 00:23:45,280 FORMALDEHYDE BECAUSE IT IS NOT 596 00:23:45,280 --> 00:23:47,480 DATED THERMODYNAMICALLY, THAT IS 597 00:23:47,480 --> 00:23:50,080 PH 7 OR ANY OTHER PH YOU WISH TO 598 00:23:50,080 --> 00:23:52,040 CHOOSE. THE REDOX POTENTIAL OF 599 00:23:52,040 --> 00:23:57,960 GAS DEPENDS ON PH. PH 11 IS THE 600 00:23:57,960 --> 00:24:00,640 -- PH OFFER THESE FLUIDS, THAT 601 00:24:00,640 --> 00:24:02,680 MAKES HYDROGEN MORE REACTIVE, 602 00:24:02,680 --> 00:24:06,360 THE REDOX POTENTIALS IS 603 00:24:06,360 --> 00:24:07,640 BASICALLY 60 MILIVOLETS PER PH 604 00:24:07,640 --> 00:24:10,680 UNIT SO CERTAINLY MORE REDUCING. 605 00:24:10,680 --> 00:24:12,600 CO 2 IN ACIDIC ENVIRONMENT IS 606 00:24:12,600 --> 00:24:14,920 EASIER TO PUSH ELECTRONS INTO IT 607 00:24:14,920 --> 00:24:16,840 SO IT IS DOWNHILL, SPONTANEOUS 608 00:24:16,840 --> 00:24:19,360 GOING TO HAPPEN, YOU HAVE BROKEN 609 00:24:19,360 --> 00:24:21,320 DOWN THE ENERGETIC BARRIER TO 610 00:24:21,320 --> 00:24:23,280 REACTION BETWEEN HYDROGEN AND CO 611 00:24:23,280 --> 00:24:24,840 2 THEY ARE BUBBLING OUT OF THE 612 00:24:24,840 --> 00:24:27,200 GROUND CO 2 COMING IN FROM OCEAN 613 00:24:27,200 --> 00:24:29,320 WORTH OF CO 2 AND JUST LOWERED 614 00:24:29,320 --> 00:24:31,120 THE BARRIER TO THEIR REACTION. 615 00:24:31,120 --> 00:24:33,480 SO HIGHER PROPORTION WILL REACT 616 00:24:33,480 --> 00:24:36,280 TO FORM, THE MOLECULES OF LIFE 617 00:24:36,280 --> 00:24:39,000 KREBS CYCLE INTERMEDIAS SO YOU 618 00:24:39,000 --> 00:24:40,680 NEED A -- INTERMEDIATES. YOU 619 00:24:40,680 --> 00:24:42,200 NEED A BARRIER AND SOMETHING 620 00:24:42,200 --> 00:24:44,360 CROSSING IT, YOU SHOW ELECTRONS 621 00:24:44,360 --> 00:24:45,800 CROSSING THE BARRIER, MAYBE 622 00:24:45,800 --> 00:24:47,600 PROTONS THE OTHER WAY. THIS WAS 623 00:24:47,600 --> 00:24:50,200 FROM A EXPERIMENT DONE BY FORMER 624 00:24:50,200 --> 00:24:52,720 Ph.D. STUDENT REUBEN HUDSON. I 625 00:24:52,720 --> 00:24:54,280 HAVE BEEN TRYING TO DO THIS IN 626 00:24:54,280 --> 00:24:56,440 THE LAB FOR FIVE YEARS BEFORE 627 00:24:56,440 --> 00:24:58,440 THAT, I NEVER MANAGED TO GET 628 00:24:58,440 --> 00:24:59,680 CONTROLS RIGHT AND HE DID IT 629 00:24:59,680 --> 00:25:01,280 AFTER HE LEFT MY LAB. GREAT FOR 630 00:25:01,280 --> 00:25:03,120 HIM. HE WAS KIND ENOUGH TO 631 00:25:03,120 --> 00:25:05,080 INCLUDE ME ON THE PAPER BUT AID 632 00:25:05,080 --> 00:25:08,520 NOTHING TO DO WITH THE SCIENCE 633 00:25:08,520 --> 00:25:10,400 BEYOND HOW WE HAVE THE IDEAS IN 634 00:25:10,400 --> 00:25:12,760 THE FIRST PLACE. ON THE HYDROGEN 635 00:25:12,760 --> 00:25:14,880 SIDE, THE ELECTRONS ARE PASSING 636 00:25:14,880 --> 00:25:18,160 TO THE BARRIER,S SOMETHING 637 00:25:18,160 --> 00:25:20,600 DODGEY ABOUT THAT SPOT. THE 638 00:25:20,600 --> 00:25:22,480 PROTONS ARE REACTING IMMEDIATELY 639 00:25:22,480 --> 00:25:24,440 WITH HYDROXIDE IONS JUST A 640 00:25:24,440 --> 00:25:27,640 NEUTRALIZATION REACTION, GOING 641 00:25:27,640 --> 00:25:29,240 TO HAPPEN IMMEDIATELY AND GIVE 642 00:25:29,240 --> 00:25:31,320 OFF HEAT. OTHER SIDE YOU PICK UP 643 00:25:31,320 --> 00:25:34,240 ELECTRONS TO, CO 2, PICKING UP 644 00:25:34,240 --> 00:25:36,000 PROTONS TO FORM ORGANIC 645 00:25:36,000 --> 00:25:38,000 MOLECULES, FORMIC ACID IN THAT 646 00:25:38,000 --> 00:25:40,680 CASE, MAYBE NOT QUITE LIKE H 647 00:25:40,680 --> 00:25:42,560 WITH PROTONS THE OTHER WAY, A 648 00:25:42,560 --> 00:25:44,680 QUESTION FOR DISCUSSION 649 00:25:44,680 --> 00:25:45,560 AFTERWARD IF INTERESTED. THIS 650 00:25:45,560 --> 00:25:47,040 HEARSAY THE SETUP IN MY LAB, 651 00:25:47,040 --> 00:25:50,680 THIS HAS TO BE DONE INSIDE AN AN 652 00:25:50,680 --> 00:25:52,640 AEROBIC BOX, THIS IS SPATIALLY, 653 00:25:52,640 --> 00:25:54,200 THE TWO POST-DOCS DOING THIS IN 654 00:25:54,200 --> 00:25:56,800 MY LAB, THIS IS A MICROFLUIDIC 655 00:25:56,800 --> 00:25:59,840 CHIP BUT WE HAVE LAMINAR FLOW, 656 00:25:59,840 --> 00:26:01,280 ACID FLOW THAT PRECIPITATES 657 00:26:01,280 --> 00:26:03,200 BARRIER IN THE MIDDLE AND THE 658 00:26:03,200 --> 00:26:04,880 QUESTION IS WHETHER THAT DRIVE 659 00:26:04,880 --> 00:26:07,000 CO 2 REDUCTION TO FORM ORGANIC 660 00:26:07,000 --> 00:26:09,200 MOLECULES? THE ANSWER IS YES, 661 00:26:09,200 --> 00:26:11,320 NOT IN HUGE AMOUNTS MIGHT NOT BE 662 00:26:11,320 --> 00:26:18,440 IMPRESS WITH THAT BUT THIS IS 663 00:26:18,440 --> 00:26:23,200 FORMATE HERE, AND ACETATE, TINY 664 00:26:23,200 --> 00:26:25,840 AMOUNTS OF METHANOL, PYRUVATE 665 00:26:25,840 --> 00:26:34,360 TOO BUT NOT ON A REGULAR BASI B. 666 00:26:34,360 --> 00:26:36,920 SO IT WORKS. IT DOESN'T WORK IN 667 00:26:36,920 --> 00:26:42,760 A HUGE WAY BUT H IS ATMOSPHERIC 668 00:26:42,760 --> 00:26:44,920 PRESSURE, OTHER WORK FROM TOM 669 00:26:44,920 --> 00:26:46,520 COLLIN'S GROUP FROM 20 YEARS AGO 670 00:26:46,520 --> 00:26:48,560 WHICH WORKED IN A STEEL REACTOR 671 00:26:48,560 --> 00:26:49,760 BUT NOT GLASS INTERESTINGLY SO 672 00:26:49,760 --> 00:26:51,800 IT IS PARTIALLY NOT QUITE 673 00:26:51,800 --> 00:26:53,320 BELIEVABLE BUT WHAT THEY START 674 00:26:53,320 --> 00:26:54,560 WITH IN THIS CASE WAS HIGH 675 00:26:54,560 --> 00:26:57,520 TEMPERATURES, HIGH PRESSURE, AND 676 00:26:57,520 --> 00:26:59,600 FORMIC ACID INSTEAD OF HYDROGEN 677 00:26:59,600 --> 00:27:02,160 CO 2, IDEA WAS HAVE THE 678 00:27:02,160 --> 00:27:04,360 DISPROPORTION NATION OF FOR MATE 679 00:27:04,360 --> 00:27:06,440 TO FORM HYDROGEN AND CO 2 WHICH 680 00:27:06,440 --> 00:27:08,600 REACT TO FORM LONG CHAIN HYDRO 681 00:27:08,600 --> 00:27:10,720 CARBONS AND LIPIDS. I DON'T KNOW 682 00:27:10,720 --> 00:27:12,120 IF THIS IT SEEMS TO ME OR IF 683 00:27:12,120 --> 00:27:14,720 THIS IS THE PROJECTOR. THE 684 00:27:14,720 --> 00:27:17,040 NUMBERS YOU CAN SEE THERE, 15, 685 00:27:17,040 --> 00:27:20,160 THE NUMBER OF CARBON ATOMS IN A 686 00:27:20,160 --> 00:27:22,920 HYDRO CARBON CHAIN. I'M GOING TO 687 00:27:22,920 --> 00:27:24,840 COME OVER HERE AND SEE IF IT 688 00:27:24,840 --> 00:27:26,480 STOPS FLASHING IF I STAND HERE 689 00:27:26,480 --> 00:27:31,320 FOR A WHILE. SO YOU CAN GET 690 00:27:31,320 --> 00:27:32,600 RELATIVELY LONG CHAIN FATTY 691 00:27:32,600 --> 00:27:35,280 ACIDS FORMING IN THOSE UNDER 692 00:27:35,280 --> 00:27:38,240 THOSE CONDITIONS. WE TOOK 693 00:27:38,240 --> 00:27:39,880 SAMPLES OF THOSE, MIXED TOGETHER 694 00:27:39,880 --> 00:27:41,840 AND LOOKED TO SEE CAN WE MAKE 695 00:27:41,840 --> 00:27:43,880 UNDER THESE CONDITIONS STARTING 696 00:27:43,880 --> 00:27:45,840 WITH THOSE PROTO CELLS UNDER THE 697 00:27:45,840 --> 00:27:48,080 HARSH CONDITIONS IN HYDRO 698 00:27:48,080 --> 00:27:48,920 THERMAL VENT? 699 00:27:48,920 --> 00:27:50,440 I WON'T GO THROUGH THE DELL 700 00:27:50,440 --> 00:27:56,000 TAILS ON DETAIL, NOT JUST ME. I 701 00:27:56,000 --> 00:27:57,120 WILL COME BACK OVER HERE IN THAT 702 00:27:57,120 --> 00:28:02,280 CASE. ALL I WANT TO TAKE HOME 703 00:28:02,280 --> 00:28:05,600 FROM THIS 70 CENTIGRADE MODERN 704 00:28:05,600 --> 00:28:08,720 NOTION -- THIS IS GOT CALCIUM 705 00:28:08,720 --> 00:28:10,720 MAGNESIUM IONS AN STRONGLY 706 00:28:10,720 --> 00:28:14,760 ALKALINE PH 12. CRYOELECTRON 707 00:28:14,760 --> 00:28:18,280 MICROSCOPY AND CONFOCAL 708 00:28:18,280 --> 00:28:19,280 MICROSCOPY, BASICALLY PICTURES 709 00:28:19,280 --> 00:28:21,880 YOU CAN SEE THE OPTICAL DENSITY 710 00:28:21,880 --> 00:28:26,360 THESE ARE MIXTURES OF FATTY 711 00:28:26,360 --> 00:28:28,320 ACIDS AND LONG CHAIN FATTY 712 00:28:28,320 --> 00:28:30,200 ALCOHOLS FORMING BIOLAYER 713 00:28:30,200 --> 00:28:33,120 MEMBRANE AROUND IT AND AQUEOUS 714 00:28:33,120 --> 00:28:35,320 INTERIOR UNDER THE HARSH 715 00:28:35,320 --> 00:28:36,560 ALKALINE HYDRO THERMAL 716 00:28:36,560 --> 00:28:46,600 CONDITIONS. THE OTHER THING -- 717 00:28:46,600 --> 00:28:49,320 THANK YOU. SO THE OTHER THING 718 00:28:49,320 --> 00:28:52,280 YOU WOULD REQUIRE FOR CO 2 719 00:28:52,280 --> 00:28:54,800 FIXATION INSIDE PROTO CELLS 720 00:28:54,800 --> 00:28:57,400 WOULD BE SOMETHING LIKETHER RA 721 00:28:57,400 --> 00:28:59,520 DOCK SIN, IRON SULFUR PROTEINS 722 00:28:59,520 --> 00:29:01,640 WE HAVE THE IRON SULFUR MINERALS 723 00:29:01,640 --> 00:29:03,560 IN BARRIERS HOW WE GO FROM 724 00:29:03,560 --> 00:29:05,160 MINERAL TO MORE LIKE A PROTEIN 725 00:29:05,160 --> 00:29:08,760 NEXT TO MEMBRANE? THE ANSWER IS 726 00:29:08,760 --> 00:29:10,760 IRON SULFUR CLUSTERS, CAN WE 727 00:29:10,760 --> 00:29:12,440 MAKE SOMETHING MORE LIKE IRON 728 00:29:12,440 --> 00:29:15,000 SULFUR CLUSTER, AND I WAS 729 00:29:15,000 --> 00:29:18,440 SHOCKED TO SEE THIS SHOULDER 730 00:29:18,440 --> 00:29:21,080 WHICH IS OR HERE YOU CAN SEE IT 731 00:29:21,080 --> 00:29:25,160 SLIGHTLY BETTER. THAT IS ON UV 732 00:29:25,160 --> 00:29:29,320 SPECK TROUGHSSCOPY, IT IS THE 733 00:29:29,320 --> 00:29:35,520 CLASSIC 4FV 4S CLUSTER SO 734 00:29:35,520 --> 00:29:37,560 CYSTEINE WITH IRON CHLORIDE AND 735 00:29:37,560 --> 00:29:41,840 SODIUM SULFIDE GIVES RISE TO 736 00:29:41,840 --> 00:29:44,000 4FE. WE DID MASS SPECTROSCOPY 737 00:29:44,000 --> 00:29:46,720 AND LOOKED AT THE REDOX 738 00:29:46,720 --> 00:29:52,400 POTENTIAL, IT IS THE SAME AS 739 00:29:52,400 --> 00:29:55,520 MINUS 450 MILIVOLTS SO THE SAME 740 00:29:55,520 --> 00:29:57,080 REDUCTION POTENTIALS. WE 741 00:29:57,080 --> 00:29:59,680 HAVEN'T SHOWNED IN CO 2 BUT IN 742 00:29:59,680 --> 00:30:01,680 PRINCIPLE SHOULD AND COULD. 743 00:30:01,680 --> 00:30:03,600 SIMPLE MIXTURE OF THE SIMPLEST 744 00:30:03,600 --> 00:30:08,680 AMINO ACIDS, AND SOME IRONS ARE 745 00:30:08,680 --> 00:30:12,360 CAPABLE ARE CAPABLE OF MOVING 746 00:30:12,360 --> 00:30:16,440 CLUSTERS IN CO 2 IN MODERN FIXED 747 00:30:16,440 --> 00:30:17,520 CELLS. SO EXTRAORDINARY THAT 748 00:30:17,520 --> 00:30:19,000 THAT WORKS. I HARDLY NAILED THE 749 00:30:19,000 --> 00:30:20,680 CASE BUT WHAT I HAVE SHOWN YOU 750 00:30:20,680 --> 00:30:23,000 IS THAT CO 2 AND HYDROGEN CAN BE 751 00:30:23,000 --> 00:30:26,760 MADE TO REACT BY PH GRADIENTS 752 00:30:26,760 --> 00:30:29,120 WITH IRON SULFUR MINERALS THAT 753 00:30:29,120 --> 00:30:31,040 GIVE RISE IN PRINCIPLE TO 754 00:30:31,040 --> 00:30:34,880 ORGANICS INCLUDING LONG CHAIN 755 00:30:34,880 --> 00:30:37,760 CAR BOXIC ACID TO MAKE IRON 756 00:30:37,760 --> 00:30:40,320 SULFUR CLUSTERS TO DRIVE CO 2 757 00:30:40,320 --> 00:30:41,480 FIXATION INSIDE THE CELLS SO A 758 00:30:41,480 --> 00:30:44,800 LOT OF MISSING HOLES THERE. BUT 759 00:30:44,800 --> 00:30:48,160 THERE IS ALSO A FEW MARKERS OF A 760 00:30:48,160 --> 00:30:50,600 POSSIBLE PATH THAT I WOULD SAY 761 00:30:50,600 --> 00:30:51,800 IT IS WORTH CONTINUE MANAGE THE 762 00:30:51,800 --> 00:30:52,720 LAB WITH THESE EXPERIMENTS 763 00:30:52,720 --> 00:30:54,960 BECAUSE I THIS I WE CAN NAIL IT 764 00:30:54,960 --> 00:30:59,920 BUT I AM ALSO PRONE TO SEL 765 00:30:59,920 --> 00:31:02,800 SELF-DELUSION. WHO CAN SAY, 766 00:31:02,800 --> 00:31:04,280 METABOLISM. SORRY ABOUT THIS. IT 767 00:31:04,280 --> 00:31:09,560 IS NOT AS CO COMPLICATED AS IT 768 00:31:09,560 --> 00:31:11,040 LOOKS. ONLY COUPLE OF THINGS TO 769 00:31:11,040 --> 00:31:12,400 NOTICE. THE IT IS CORE OF 770 00:31:12,400 --> 00:31:14,160 METABOLISM AS WE KNOW IT. I 771 00:31:14,160 --> 00:31:15,720 WOULD SAY IT IS OLDER AN GENES, 772 00:31:15,720 --> 00:31:18,960 I SAY THAT BECAUSE BACTERIA HAVE 773 00:31:18,960 --> 00:31:22,400 THE SAME CHEMISTRY GOING ON BUT 774 00:31:22,400 --> 00:31:24,920 THE GENES THAT CODE THE ENZYMES 775 00:31:24,920 --> 00:31:26,920 THAT CATALYZE ARE NOT CONSERVED 776 00:31:26,920 --> 00:31:29,600 IN BACTERIA AND ARCHEIIA SO YOU 777 00:31:29,600 --> 00:31:30,440 HAVE DIFFERENT GENES THAT 778 00:31:30,440 --> 00:31:34,640 CATALYZE THE SAME CHEMISTRY. 779 00:31:34,640 --> 00:31:36,160 EAST YESTERDAYS EXPLANATION IS 780 00:31:36,160 --> 00:31:36,920 CHEMISTRY CAME BEFORE THE EVEN 781 00:31:36,920 --> 00:31:38,640 GOOS WHICH IS A SWAGGERING CLAIM 782 00:31:38,640 --> 00:31:40,280 BUT LOOK WHAT IS GOING ON HERE 783 00:31:40,280 --> 00:31:42,560 IN BROWN WE HAVE HYDRO WREN SO 784 00:31:42,560 --> 00:31:46,000 CO 2 TOP LEFT HAND CORNER IN 785 00:31:46,000 --> 00:31:47,880 BROWN ORANGE COLOR, HYDROGEN 786 00:31:47,880 --> 00:31:51,560 BEING GREEN WE HAVE CO 2 AND 787 00:31:51,560 --> 00:31:54,040 TAKE NOTICE STRAIGHT TO THE 788 00:31:54,040 --> 00:31:56,880 CENTS CYCLE, ACETYLCOA IT COULD 789 00:31:56,880 --> 00:32:01,280 BE BOUND TO MINERAL SURFACE OR 790 00:32:01,280 --> 00:32:04,800 BOUND ON ACETATE. PYRUVATE, 791 00:32:04,800 --> 00:32:06,640 ALPHA KETO GLUTERATE, A FEW 792 00:32:06,640 --> 00:32:08,240 STEPS BEFORE WE ARE AT THE HEART 793 00:32:08,240 --> 00:32:10,920 OF METABOLISM, IT IS THE 794 00:32:10,920 --> 00:32:13,120 CHEMISTRY OF HYDROGEN AND CO 2 795 00:32:13,120 --> 00:32:14,840 AND LITTLE ELSE. SOME AMOAN YAW 796 00:32:14,840 --> 00:32:17,320 TO GET O THE AMINO ACIDS. SO NOT 797 00:32:17,320 --> 00:32:20,840 A LONG WAY. MOST -- THE BLUE 798 00:32:20,840 --> 00:32:21,880 ARROWS BEING DONE IN THE LAB 799 00:32:21,880 --> 00:32:23,400 OVER THE LAST SEVEN OR EIGHT 800 00:32:23,400 --> 00:32:26,440 YEARS. NONE OF THAT WAS DONE 801 00:32:26,440 --> 00:32:31,640 EIGHT YEARS AGO BUT LAST 7, 8 802 00:32:31,640 --> 00:32:33,360 YEARS,S CENTS CYCLE 803 00:32:33,360 --> 00:32:37,280 GLYCOGENESIS, THE ACETYLCOA 804 00:32:37,280 --> 00:32:38,040 PATHWAY ARE NONE IN THE LAB 805 00:32:38,040 --> 00:32:40,720 UNDER CONDITIONS WITH METAL IONS 806 00:32:40,720 --> 00:32:42,240 AS CATALYSTS WITH THE STEPS YOU 807 00:32:42,240 --> 00:32:44,240 SEE IN MODERN PATHWAYS AND THE 808 00:32:44,240 --> 00:32:48,480 CENTS CYCLE IS NOT CLOSED AND 809 00:32:48,480 --> 00:32:53,920 COMPLETE 9 OF 10 REACTIONS ARE 810 00:32:53,920 --> 00:32:56,000 DONE IN THE LAB NOW BY THREE OR 811 00:32:56,000 --> 00:32:57,800 FOUR DIFFERENT GROUPS. IT IS NO 812 00:32:57,800 --> 00:33:02,200 LONGER HAND WAVIN WAVING. IT ISL 813 00:33:02,200 --> 00:33:04,160 CHEMISTRY. THE IT WILL HAPPEN IN 814 00:33:04,160 --> 00:33:06,000 THE RIGHT CONDITIONS. THIS IS 815 00:33:06,000 --> 00:33:08,440 THE RED MUCH MORE DIFFICULT 816 00:33:08,440 --> 00:33:09,680 PROBLEM. YOU HAVE TO GET TO THE 817 00:33:09,680 --> 00:33:11,360 RED BOXES BEFORE YOU CAN BEGIN 818 00:33:11,360 --> 00:33:14,640 TO SYNTHESIZE NUCLEOTIDE 819 00:33:14,640 --> 00:33:15,640 BUSINESS THE BIOCHEMICAL 820 00:33:15,640 --> 00:33:17,400 PATHWAYS. WE LOOKED AT LATER 821 00:33:17,400 --> 00:33:20,760 STEPS SO THIS IS ASPAR AT A TIME 822 00:33:20,760 --> 00:33:23,280 IS A KEY AMINO ACID NEVER 823 00:33:23,280 --> 00:33:24,360 SYNTHESIZED UNDER CONDITIONS 824 00:33:24,360 --> 00:33:28,000 BEFORE. THERE IT IS. WE 825 00:33:28,000 --> 00:33:29,520 PUBLISHED THIS RECENTLY, A 826 00:33:29,520 --> 00:33:32,400 LITTLE BIT OF A CON BECAUSE WE 827 00:33:32,400 --> 00:33:34,680 STARTED WITH ACETATE ONE STOP 828 00:33:34,680 --> 00:33:36,880 BEFORE ASPAR AT A TIME. THE 829 00:33:36,880 --> 00:33:38,560 QUESTION IS COULD WE DO THAT 830 00:33:38,560 --> 00:33:43,800 STEP USING A CO-FACTOR PARADOCKS 831 00:33:43,800 --> 00:33:46,200 MEAN, WE NEED TO MAKE IT TO SHOW 832 00:33:46,200 --> 00:33:48,320 IT WORKS. BUT INTERESTING THIS 833 00:33:48,320 --> 00:33:51,280 IS WITH PARADOCKS MEAN YOU DON'T 834 00:33:51,280 --> 00:33:54,120 GET ANY ASPARTATE WITH THAT 835 00:33:54,120 --> 00:33:56,680 ALONE BUT WITH COPPER SULFATE OR 836 00:33:56,680 --> 00:33:58,320 IRON CHLORIDE YOU GET A 837 00:33:58,320 --> 00:34:00,520 REASONABLE PEAK. IT HAS TO BE 838 00:34:00,520 --> 00:34:03,280 KINETICALLY FAST. IT IS STRIKING 839 00:34:03,280 --> 00:34:04,360 METAL IRONS TURN OUT THE ONE 840 00:34:04,360 --> 00:34:06,000 WHAT IS ARE DRIVING THIS 841 00:34:06,000 --> 00:34:09,080 CHEMISTRY. THIS THIS IS ALANINE 842 00:34:09,080 --> 00:34:17,480 SO OXALLO ACETATE, THE PYRUVATE 843 00:34:17,480 --> 00:34:22,520 BECOMES CONVERTED INTO ALANINE. 844 00:34:22,520 --> 00:34:26,160 THAT HAPPENS SPONTANEOUSLY, IT 845 00:34:26,160 --> 00:34:28,200 IS FASCINATING THAT (INAUDIBLE) 846 00:34:28,200 --> 00:34:30,160 INHIBITS THAT PROCESS, PARADOX 847 00:34:30,160 --> 00:34:32,200 MEAN BY ITSELF. WE LOOKED AT 848 00:34:32,200 --> 00:34:33,520 GCMS, NOT LONG ON THIS BUT WHAT 849 00:34:33,520 --> 00:34:37,960 YOU HAVE SEEN ALANINE ASPARTATE. 850 00:34:37,960 --> 00:34:39,840 WE GET LYSINE BETA ALANINE AND 851 00:34:39,840 --> 00:34:42,760 SERINE IN TRACE AMOUNTS BUT 852 00:34:42,760 --> 00:34:44,960 INTERESTING GET -- RECOVER IING 853 00:34:44,960 --> 00:34:47,320 THE AMINO ACID PART OF 854 00:34:47,320 --> 00:34:49,720 METABOLISM, SO LOOKS LIKE 855 00:34:49,720 --> 00:34:52,040 RECOVERING THE METABOLIC MAP. I 856 00:34:52,040 --> 00:34:53,880 MENTION CYSTEINE TO MAKE 857 00:34:53,880 --> 00:34:56,240 CYSTEINE TO MAKE IRON SULFUR 858 00:34:56,240 --> 00:34:58,480 CLUSTER NOBODY MADE CYSTEINE 859 00:34:58,480 --> 00:34:59,800 UNDER THESE CONDITIONS EITHER. 860 00:34:59,800 --> 00:35:01,760 THAT IS IT HERE. THAT IS THE 861 00:35:01,760 --> 00:35:03,640 GAME, ONLY ONE STEP COMING FROM 862 00:35:03,640 --> 00:35:05,440 SERINE BUT WE MADE GLYCENE 863 00:35:05,440 --> 00:35:07,720 SERINE AND CYSTEINE WE ARE 864 00:35:07,720 --> 00:35:10,320 TRYING TO DO THAT AS ONE POT 865 00:35:10,320 --> 00:35:12,240 SYNTHESIS SO IT LOOKS THE MORE 866 00:35:12,240 --> 00:35:13,760 INTRACTABLE ARE BEGINNING TO 867 00:35:13,760 --> 00:35:15,560 HAPPEN. THIS IS ONE OF MY 868 00:35:15,560 --> 00:35:16,720 FAVORITES FROM THE LAB IN THE 869 00:35:16,720 --> 00:35:19,040 LAST YEAR, THIS IS YOUR SILL, 870 00:35:19,040 --> 00:35:21,000 THIS IS THE BIOCHEMICAL PATHWAY 871 00:35:21,000 --> 00:35:23,680 STARTING WITH AKNOWNIA AND 872 00:35:23,680 --> 00:35:31,240 CARBONATE AND ASPARTATE. THIS IS 873 00:35:31,240 --> 00:35:33,800 A ONE STOP SYNTHESIS AND 874 00:35:33,800 --> 00:35:35,600 SYNTHESIS A STEP BEFORE THATMENT 875 00:35:35,600 --> 00:35:39,440 IN THE PRESENCE ONLY METAL IONS, 876 00:35:39,440 --> 00:35:40,920 COPPER IN THIS CASE. WE TRIED 877 00:35:40,920 --> 00:35:42,200 DIFFERENT PH DIFFERENT 878 00:35:42,200 --> 00:35:45,640 TEMPERATURES, WHOLE SET OF METAL 879 00:35:45,640 --> 00:35:47,520 IONS, DIFFERENT PRESSURES AND SO 880 00:35:47,520 --> 00:35:49,640 ON. AND WE OPTIMIZE THE BEST 881 00:35:49,640 --> 00:35:52,400 CONDITIONS AND THIS IS A 882 00:35:52,400 --> 00:35:54,040 SYNTHESIS OF YOUR SILL WITHIN 883 00:35:54,040 --> 00:35:55,560 THE ONMIZED SET OF CONDITIONS 884 00:35:55,560 --> 00:35:58,040 AND GOT TENFOLD THE YIELD. I WAS 885 00:35:58,040 --> 00:36:01,440 PLEASED THAT IT TURNS OUT THE PH 886 00:36:01,440 --> 00:36:05,280 9, 90 DEGREES CENTIGRADE, IN THE 887 00:36:05,280 --> 00:36:07,160 PRESENCE OF COPPER SULFIDE OF 888 00:36:07,160 --> 00:36:12,200 ALL THINGS. SO ALKALINE HYDRO 889 00:36:12,200 --> 00:36:14,440 THERMAL CONDITIONS OPTIMIZES THE 890 00:36:14,440 --> 00:36:17,360 SYNTHESIS OF URASIL. WE HAVE 891 00:36:17,360 --> 00:36:19,720 NOT MADE ATP OR NOT MADE ADEN 892 00:36:19,720 --> 00:36:24,680 SCENE, NOT PURINE NUCLEOTIDES SO 893 00:36:24,680 --> 00:36:27,200 LOT TO DO BUT ENOUGH 894 00:36:27,200 --> 00:36:28,320 ENCOURAGEMENT TO MAKE ME THINK 895 00:36:28,320 --> 00:36:32,680 IT IS WORTH PURSUING THIS. NOT 896 00:36:32,680 --> 00:36:36,560 MADE ATP, NOT MADE ADEN SCENE 897 00:36:36,560 --> 00:36:38,360 BUT WE CAN PHOSPHORYLATE ADP TO 898 00:36:38,360 --> 00:36:39,680 ATP, THAT IS INTERESTING. 899 00:36:39,680 --> 00:36:41,680 DOESN'T REQUIRE THE ATP 900 00:36:41,680 --> 00:36:44,760 SYNTHASE, SPINNING THERE IN THE 901 00:36:44,760 --> 00:36:46,760 MIDDLE, IT CAN BE DONE WITH AS 902 00:36:46,760 --> 00:36:48,560 TILE PHOSPHATE A TWO CARBON AND 903 00:36:48,560 --> 00:36:50,880 WE GET ABOUT A 20 PERCENT YIELD. 904 00:36:50,880 --> 00:36:53,320 THIS IS QUITE OLD WORK WE 905 00:36:53,320 --> 00:36:54,920 REPEATED, IT TOOK A WHILE TO 906 00:36:54,920 --> 00:37:00,000 REPEAT BUT ONCE WE DID, WE FOUND 907 00:37:00,000 --> 00:37:02,400 TEN OTHER PHOSPHORYLATING AGENTS 908 00:37:02,400 --> 00:37:04,000 DIDN'T WORK ONLY AS TEAL 909 00:37:04,000 --> 00:37:05,520 PHOSPHATE WORKED. WE FOUND 910 00:37:05,520 --> 00:37:08,520 ABOUT TEN METAL IRONS ONLY 911 00:37:08,520 --> 00:37:11,440 (INAUDIBLE) WORKED IT WORKS FOR 912 00:37:11,440 --> 00:37:14,080 ARCDP, WE CAN PHOSPHORYLATE ADP 913 00:37:14,080 --> 00:37:18,680 TO ATP BURKS NOT GTP TO UDP SO 914 00:37:18,680 --> 00:37:21,440 WHY IS ATP UNIVERSAL ENERGY? 915 00:37:21,440 --> 00:37:22,520 BECAUSE YOU CAN MAKE IT IN 916 00:37:22,520 --> 00:37:24,680 WATER, YOU CAN PHOSPHORYLATE IT 917 00:37:24,680 --> 00:37:26,120 IN WATER WITH (INAUDIBLE) AS THE 918 00:37:26,120 --> 00:37:29,280 ONLY CATALYST, 20% YIELD. SO IT 919 00:37:29,280 --> 00:37:32,800 IS AGAIN FAVORED CHEMISTRY. IT 920 00:37:32,800 --> 00:37:35,360 WORKS BECAUSE THE GOD OF 921 00:37:35,360 --> 00:37:36,880 THERMODYNAMICS SAYS IT SHALL BE. 922 00:37:36,880 --> 00:37:41,880 IT IS ALMOST QUITE SCARY IF YOU 923 00:37:41,880 --> 00:37:45,160 THINK THAT WAY. INFORMATION. I 924 00:37:45,160 --> 00:37:47,000 HAVE INSINUATED THIS, THIS IS A 925 00:37:47,000 --> 00:37:49,280 MAP OF METABOLISM THAT MAYBE 926 00:37:49,280 --> 00:37:51,200 SLIGHTLY FAMILIAR NOW, COLOR 927 00:37:51,200 --> 00:37:53,680 CODED HERE ARE AMINO ACIDS SO 928 00:37:53,680 --> 00:37:57,040 GLYCENE, ALANINE, ASPARTATE ALL 929 00:37:57,040 --> 00:37:58,480 IN GRAY, THEY HAVE A G AT THE 930 00:37:58,480 --> 00:38:01,120 FIRST POSITION OF THEIR CODON. 931 00:38:01,120 --> 00:38:05,200 THEY ARE ALL A SINGLE STEP FROM 932 00:38:05,200 --> 00:38:07,240 CARBOXYLIC ACID. A SINGLE 933 00:38:07,240 --> 00:38:09,160 REDUCTIVE AM NATION FROM A 934 00:38:09,160 --> 00:38:11,040 CARBOXYLIC ACID TO FORM THOSE. 935 00:38:11,040 --> 00:38:12,520 THEY HAVE THE SAME GENE AT THE 936 00:38:12,520 --> 00:38:14,840 FIRST POSITION. IN YELLOW, IS 937 00:38:14,840 --> 00:38:16,560 A, THE FIRST POSITION OF THE 938 00:38:16,560 --> 00:38:21,840 CODON. IN BLUE IT IS CYTOKINE 939 00:38:21,840 --> 00:38:24,600 AND IN GREEN IT IS YOU. SO 940 00:38:24,600 --> 00:38:26,440 DOESN'T TELL AS MUMP BUT TELLS 941 00:38:26,440 --> 00:38:28,040 US THE SOME STRUCTURE, SOME 942 00:38:28,040 --> 00:38:29,800 RELATIONSHIP WEAN THE CODONS AND 943 00:38:29,800 --> 00:38:33,960 -- BETWEEN CODONS AND AUTOTROPIC 944 00:38:33,960 --> 00:38:34,440 METABOLISM LIMB WHICH IS 945 00:38:34,440 --> 00:38:37,840 INTERESTING AS A STARTING POINT. 946 00:38:37,840 --> 00:38:39,960 IF WE STRUCTURE -- SO THE TOP 947 00:38:39,960 --> 00:38:41,400 BOX THERE AT THE LEFT, THAT IS 948 00:38:41,400 --> 00:38:42,640 WITH THE G AT THE FIRST POSITION 949 00:38:42,640 --> 00:38:46,280 OF THE CODON, THEN FIRST 950 00:38:46,280 --> 00:38:48,840 POSITION, THIS IS NOW HYDRO FOE 951 00:38:48,840 --> 00:38:55,400 BUSINESSTY, SO JUST TO SHOW OWE, 952 00:38:55,400 --> 00:38:57,080 VALENE IS A -- AND THE SECOND 953 00:38:57,080 --> 00:38:59,160 POSITION OF ANTI-CODON IS A, 954 00:38:59,160 --> 00:39:00,840 WHICH IS THE MOST HYDROPHOBIC 955 00:39:00,840 --> 00:39:06,160 BASE. ASPARTATE HERE, 956 00:39:06,160 --> 00:39:10,000 HYDROPHILIC AMINO ACID BY YOU, 957 00:39:10,000 --> 00:39:11,680 THE SECOND CODON HYDROPHILIC 958 00:39:11,680 --> 00:39:13,640 BASE. THEY ARE INTEREST 959 00:39:13,640 --> 00:39:16,200 INTERACTIONS HYDROPHOBIC 960 00:39:16,200 --> 00:39:16,840 INTERACTIONS OR SOMETHING 961 00:39:16,840 --> 00:39:18,640 SIMILAR GOING ON. WORKS BEST 962 00:39:18,640 --> 00:39:19,840 WITH PURINE AT THE FIRST 963 00:39:19,840 --> 00:39:25,440 POSITION OF THE CODON, WE SEE A 964 00:39:25,440 --> 00:39:26,840 STROLL RELATIONSHIP, LESS WELL 965 00:39:26,840 --> 00:39:30,280 WITH PRIM DEA DEAN. THESE PATTEN 966 00:39:30,280 --> 00:39:31,840 SUGGEST DON'T NAIL BUT SUGGEST 967 00:39:31,840 --> 00:39:33,720 BIOPHYSICAL REACTIONS. THIS IS 968 00:39:33,720 --> 00:39:35,320 THE THIRD POSITION AND EVERYBODY 969 00:39:35,320 --> 00:39:37,360 HEAR SAY THE THIRD POSITION IS 970 00:39:37,360 --> 00:39:39,440 REDUNDANT. THERE IS NO PATTERN 971 00:39:39,440 --> 00:39:41,280 THERE BUT WILL IS. THIS IS JUST 972 00:39:41,280 --> 00:39:43,680 TO GIVE ONE EXAMPLE AGAIN, THIS 973 00:39:43,680 --> 00:39:46,280 IS AN INVERTED CODON TABLE, THIS 974 00:39:46,280 --> 00:39:48,480 IS A G THE FIRST POSITION, A AT 975 00:39:48,480 --> 00:39:49,640 THE SECOND POSITION OF THE 976 00:39:49,640 --> 00:39:54,400 CODON, THAT IS TRUE FOR 977 00:39:54,400 --> 00:39:55,840 ASPARTATE AND GLUTAMATE BUT A 978 00:39:55,840 --> 00:39:57,160 PRIM DEAN AT THIRD POSITION OF 979 00:39:57,160 --> 00:39:59,760 CODON. AND INVERT FORD THE 980 00:39:59,760 --> 00:40:01,240 UNDERCODON. THE DIFFERENCE IS 981 00:40:01,240 --> 00:40:03,640 SIZE. IF THERE IS A SMALL PRIM 982 00:40:03,640 --> 00:40:05,120 DEAN AT THIRD POSITION OF 983 00:40:05,120 --> 00:40:06,720 ANTI-CODON YOU HAVE LARGER AMINO 984 00:40:06,720 --> 00:40:08,480 ACID THERE AND VICE VERSA, IF 985 00:40:08,480 --> 00:40:11,200 YOU GO TO LARGE PURINE THAT 986 00:40:11,200 --> 00:40:12,120 THIRD POSITION ANTI-CODON YOU 987 00:40:12,120 --> 00:40:14,440 HAVE A SMALLER AMINO ACID THERE. 988 00:40:14,440 --> 00:40:17,240 SO THESE PATTERNS ALL -- DON'T 989 00:40:17,240 --> 00:40:19,880 NAIL ANYTHING BUT SAY THERE ARE 990 00:40:19,880 --> 00:40:27,680 DIRECT INTERACTIONS GOING ON. 991 00:40:27,680 --> 00:40:33,000 WRONG DIRECTION HERE. THIS SLIDE 992 00:40:33,000 --> 00:40:36,160 IS OUT OF PLACE. GOING TO P WHO 993 00:40:36,160 --> 00:40:39,640 TO THAT ONE. DON'T KNOW HOW THAT 994 00:40:39,640 --> 00:40:41,040 HAPPENED. THIS IS MOLECULAR 995 00:40:41,040 --> 00:40:43,360 DYNAMIC SIMULATIONS IN THE LAB. 996 00:40:43,360 --> 00:40:46,160 OVER LAST YEAR OR SO. AND SO 997 00:40:46,160 --> 00:40:47,920 JUST TO SHOW YOU HERE, SO THIS 998 00:40:47,920 --> 00:40:51,400 IS THE PROPORTION OF TIME SPENT 999 00:40:51,400 --> 00:40:53,040 BY PROLINE NEXT TO ONE OF THE 1000 00:40:53,040 --> 00:40:57,440 FOUR BASES AMP CMP GMP OR UMP AN 1001 00:40:57,440 --> 00:40:59,280 IT SPENDS TIME BIG PEAK HERE 1002 00:40:59,280 --> 00:41:03,000 NEXT TO GMP WHICH IS THE BASE 1003 00:41:03,000 --> 00:41:06,480 THAT CODES FOR IT. THE SECULAR 1004 00:41:06,480 --> 00:41:07,560 POSITION OF THE ANTI-CODON 1005 00:41:07,560 --> 00:41:09,360 SUGGESTING A RELATIONSHIP THERE. 1006 00:41:09,360 --> 00:41:11,920 WE GETS -- WE DO BETTER THAN 99% 1007 00:41:11,920 --> 00:41:14,400 OF RANDOM ALLOCATION SO WE CAN 1008 00:41:14,400 --> 00:41:16,080 PREDICT 50% OF THE ANTI-CODONS 1009 00:41:16,080 --> 00:41:18,760 FROM MOLECULAR DYNAMICS AND 1010 00:41:18,760 --> 00:41:21,920 RELATIONS. WE CAN DO SAME THING 1011 00:41:21,920 --> 00:41:24,280 WITH ONLY DOING FIVE AMINO ACIDS 1012 00:41:24,280 --> 00:41:27,000 SO FAR, THIS IS NMR, BINDING 1013 00:41:27,000 --> 00:41:28,280 STRENGTH AND INTERACTIONS WITH 1014 00:41:28,280 --> 00:41:30,840 NMR, SHOWING THE SAME THING, THE 1015 00:41:30,840 --> 00:41:32,600 INTERACTIONS ARE STRONGEST 1016 00:41:32,600 --> 00:41:33,920 BETWEEN NUCLEOTIDE THAT CODES 1017 00:41:33,920 --> 00:41:36,480 FOR AMINO ACID AND THE AMINO 1018 00:41:36,480 --> 00:41:40,360 ACID ITSELF. I HAVE HOPPED A 1019 00:41:40,360 --> 00:41:42,680 SLIDE BUT I WILL LEAVE THAT 1020 00:41:42,680 --> 00:41:48,240 SLIDE BEHIND. AND MOVE ON. WHAT 1021 00:41:48,240 --> 00:41:50,640 DOES THAT SHOW? IN MY MIND THAT 1022 00:41:50,640 --> 00:41:53,960 SHOWS THAT CO 2 FIXATION CAN BE 1023 00:41:53,960 --> 00:41:55,280 DRIVEN TO GIVE RISE TO 1024 00:41:55,280 --> 00:41:56,680 METABOLISM WHICH IS CAPABLE OF 1025 00:41:56,680 --> 00:41:58,320 POTENTIALLY GIVING RISE TO 1026 00:41:58,320 --> 00:42:00,200 NUCLEOTIDE WHICH WILL INTERACT 1027 00:42:00,200 --> 00:42:03,040 WITH AMINO ACIDS IN A WAY WHICH 1028 00:42:03,040 --> 00:42:05,400 PREFIGURES THE CODE AND GENES 1029 00:42:05,400 --> 00:42:06,520 ARE THERE ARE LIKELY TO ARISE IN 1030 00:42:06,520 --> 00:42:10,480 THE CONTEXT OF A AUTO TROPIC 1031 00:42:10,480 --> 00:42:12,320 METABOLISM GROWING PROTO CELLS 1032 00:42:12,320 --> 00:42:14,000 SO NOT UNREASONABLE CONTEXT FOR 1033 00:42:14,000 --> 00:42:17,320 THE ORIGIN OF LIFE LIFE. MAY OY 1034 00:42:17,320 --> 00:42:19,120 NOT BE REAL BUT ENOUGH SUBSTANCE 1035 00:42:19,120 --> 00:42:21,120 TO MAKE IT LOOK PLAUSIBLE OR 1036 00:42:21,120 --> 00:42:22,360 FEASIBLE. SO WHY ANY OF THAT 1037 00:42:22,360 --> 00:42:27,680 MATTER? TO YOU? LET'S FAST 1038 00:42:27,680 --> 00:42:29,840 FORWARD AROUND 3 1/2 BILLION 1039 00:42:29,840 --> 00:42:32,320 YEARS TO THE EXPLOSION WHERE WE 1040 00:42:32,320 --> 00:42:35,400 SEE FIRST ANIMALS IN -- NOT THE 1041 00:42:35,400 --> 00:42:37,440 FIRST ANIMALS THESE ARE THE 1042 00:42:37,440 --> 00:42:40,440 LEFT-HAND SIDE, THESE ARE FILTER 1043 00:42:40,440 --> 00:42:41,640 CREATURES MORE STUCK TO THE 1044 00:42:41,640 --> 00:42:45,600 BOTTOM OF THE OCEAN, OFTEN 200 1045 00:42:45,600 --> 00:42:47,360 METERS DOWN IN BLACKNESS MEANING 1046 00:42:47,360 --> 00:42:50,120 NOT PHOTO SYNTHETIC THEY LOOK 1047 00:42:50,120 --> 00:42:52,360 LIKE PLANTS BUT NOT, THEY ARE A 1048 00:42:52,360 --> 00:42:55,920 BIT LIKE SPONGES. THEN WE HAVE A 1049 00:42:55,920 --> 00:42:58,680 EXPLOSION, WHAT WE ARE SEEING IS 1050 00:42:58,680 --> 00:43:00,600 REALLY PREDATION, WE ARE SEEING 1051 00:43:00,600 --> 00:43:06,200 CLAWS AN EYES YOU WILL KINDS OF 1052 00:43:06,200 --> 00:43:09,200 ARMER PLATING, WE ARE SEEING 1053 00:43:09,200 --> 00:43:11,040 PREDATORS PREY, MODERN ECO 1054 00:43:11,040 --> 00:43:13,200 SYSTEMS AS WE UNDERSTAND IT. TO 1055 00:43:13,200 --> 00:43:15,280 RUN AROUND AND DO THOSE THINGS 1056 00:43:15,280 --> 00:43:18,400 WE CAN BE VIRTUALLY CERTAIN THAT 1057 00:43:18,400 --> 00:43:20,280 THEY WERE AEROBIC, QUITE A LOT 1058 00:43:20,280 --> 00:43:22,160 OF EVIDENCE THAT OXYGEN WAS 1059 00:43:22,160 --> 00:43:24,240 ARISING IN THE ATMOSPHERE AROUND 1060 00:43:24,240 --> 00:43:26,320 THAT TIME BECAUSE AEROBIC 1061 00:43:26,320 --> 00:43:27,280 RESPIRATION GIVES ENOUGH POWER 1062 00:43:27,280 --> 00:43:34,000 TO HAVE THAT MANY TROPIC LEVELS. 1063 00:43:34,000 --> 00:43:37,000 SO ROUGHLY 40% EFFICIENCY YOU 1064 00:43:37,000 --> 00:43:39,120 GET 40% ENERGY FROM WHATEVER 1065 00:43:39,120 --> 00:43:40,560 YOU'S, YOU CAN CONSERVE THAT. 1066 00:43:40,560 --> 00:43:44,440 THAT ALLOWS YOU AROUND 6 TROPIC 1067 00:43:44,440 --> 00:43:46,440 LEVELS IF YOU JUST TAKE A RANDOM 1068 00:43:46,440 --> 00:43:48,400 STAB IN THE DARK AND SAY YOU 1069 00:43:48,400 --> 00:43:50,640 NEED 1% ENERGY AVAILABLE IN THE 1070 00:43:50,640 --> 00:43:52,120 SYSTEM PASS THROUGH, YOU CAN 1071 00:43:52,120 --> 00:43:54,000 HAVE SIX TROPIC LEVELS WITH 1072 00:43:54,000 --> 00:43:56,040 RESERVATION. SOMETHING LIKE 1073 00:43:56,040 --> 00:44:00,280 FERMENTATION OR ANY OTHER 1074 00:44:00,280 --> 00:44:01,640 ELECTRON ACCEPTORS THERE IS NOT 1075 00:44:01,640 --> 00:44:03,520 OXYGEN THEY TEN NOT TO 1076 00:44:03,520 --> 00:44:05,840 ACCUMULATE IN ABSENCE OF OXYGEN, 1077 00:44:05,840 --> 00:44:08,080 YOU ONLY GET TWO OR THREE TROPIC 1078 00:44:08,080 --> 00:44:10,560 LEVEL WHICH IS MEANS YOU CAN'T 1079 00:44:10,560 --> 00:44:11,400 HAVE PREDATION IN THE ABSENCE OF 1080 00:44:11,400 --> 00:44:17,200 A MODERN AEROBIC RESPIRATORY 1081 00:44:17,200 --> 00:44:18,800 SYSTEM. YOU CAN BE CERTAIN THE 1082 00:44:18,800 --> 00:44:21,640 ANIMALS HAD A MODERN KREBS CYCLE 1083 00:44:21,640 --> 00:44:23,280 AS WE KNOW IT. AND THE 1084 00:44:23,280 --> 00:44:25,040 SURPRISING THING THERE IS WHAT 1085 00:44:25,040 --> 00:44:27,440 WE START OUT WITH ESSENTIALLY 1086 00:44:27,440 --> 00:44:30,520 COUPLE OF THESE SLIDES OUT OF 1087 00:44:30,520 --> 00:44:35,360 ORDER. WE START WITH REDUCTIVE 1088 00:44:35,360 --> 00:44:36,600 KREBS CYCLE ON THE LEFT HAHN 1089 00:44:36,600 --> 00:44:37,960 SIDE I SHOWED YOU AT THE 1090 00:44:37,960 --> 00:44:39,760 BEGINNING BASICALLY A 1091 00:44:39,760 --> 00:44:42,280 BIOSYNTHETIC ENGINE MAKING 1092 00:44:42,280 --> 00:44:43,520 ORGANICS, THE RIGHT HAND SIDE WE 1093 00:44:43,520 --> 00:44:46,200 HAVE THE OXIDATIVE KREBS CYCLE, 1094 00:44:46,200 --> 00:44:50,280 BURNING THOSE ORGANICS TO 1095 00:44:50,280 --> 00:44:52,600 GENERATE MEMBRANE POTENTIAL. YOU 1096 00:44:52,600 --> 00:44:54,720 WONDER WELL, FOR THE FIRST TWO 1097 00:44:54,720 --> 00:44:56,520 BILLION YEARS OR MORE OF LIFE WE 1098 00:44:56,520 --> 00:45:01,080 HAVE GOT -- WE HAVE THESE 1099 00:45:01,080 --> 00:45:03,440 CRYOSEN SYNTHETIC ENGINES MAKING 1100 00:45:03,440 --> 00:45:05,320 MOLECULES THEN IT SCREECHES TO A 1101 00:45:05,320 --> 00:45:07,000 HALT AND CHANGES DIRECTIONS? 1102 00:45:07,000 --> 00:45:08,400 CAN'T BE DOING THAT. HOW DOES IT 1103 00:45:08,400 --> 00:45:11,880 CHANGE? THESE SLIDES ARE OUT OF 1104 00:45:11,880 --> 00:45:17,360 ORDER. THIS IS A INSIGHT INTO 1105 00:45:17,360 --> 00:45:18,240 HOW IT HAPPENS BECAUSE THIS 1106 00:45:18,240 --> 00:45:20,000 HAPPENS IN MOST BACTERIA, THAT I 1107 00:45:20,000 --> 00:45:21,680 DON'T HAVE A COMPLETE CENTS 1108 00:45:21,680 --> 00:45:23,320 PSYCH MILLION THE WAY WE 1109 00:45:23,320 --> 00:45:26,120 RECOGNIZE IT. THEY HAVE THEY ARE 1110 00:45:26,120 --> 00:45:27,920 A TWO PRONGED PATHWAY, THEY HAVE 1111 00:45:27,920 --> 00:45:30,120 AN OXIDATIVE PRONG AT THE TOP 1112 00:45:30,120 --> 00:45:31,600 AND PULLING OUT HYDROGEN HERE IN 1113 00:45:31,600 --> 00:45:33,520 THE WAY OF A MODERN SYSTEM, BUT 1114 00:45:33,520 --> 00:45:35,080 THEY ALSO HAVE A REDUCTIVE 1115 00:45:35,080 --> 00:45:39,840 PRONG. THIS GOES BACK OF COURSE 1116 00:45:39,840 --> 00:45:42,600 TO (INAUDIBLE) SAINT GEORGE AND 1117 00:45:42,600 --> 00:45:44,920 KREBS HIMSELF IN 190s WHO KNEW 1118 00:45:44,920 --> 00:45:47,760 VERY -- 1930s, WHO KNEW THAT 1119 00:45:47,760 --> 00:45:49,520 IT GIVES RISE TO SUCCINATE AND 1120 00:45:49,520 --> 00:45:53,520 SO ON. IT CAN BE OPERATING 1121 00:45:53,520 --> 00:45:55,040 EITHER DIRECTION ON THAT PART OF 1122 00:45:55,040 --> 00:45:57,320 THE PATHWAY. SO IT IS REDUCTION 1123 00:45:57,320 --> 00:45:59,560 BALANCE, NADH AND REDUCTION, 1124 00:45:59,560 --> 00:46:01,560 WHETHER YOU ARE SUCKING IN 1125 00:46:01,560 --> 00:46:02,720 HYDROGENS OR SPITTING THEM OUT 1126 00:46:02,720 --> 00:46:04,280 AND BURNING THEM. THIS PART HERE 1127 00:46:04,280 --> 00:46:07,600 IS THE INTERESTING BIT BECAUSE 1128 00:46:07,600 --> 00:46:09,040 IT POINTS TO SUCCINATE. WHAT IS 1129 00:46:09,040 --> 00:46:11,040 HAPPENING THERE? DOES IT GO THAT 1130 00:46:11,040 --> 00:46:13,080 WHICHER THIS WAY? A COMPLETE 1131 00:46:13,080 --> 00:46:15,280 SICKLE OR NOTHING AT ALL? 1132 00:46:15,280 --> 00:46:17,080 SUCCINATE IS CENTRAL TO HOW THAT 1133 00:46:17,080 --> 00:46:21,680 WORKS. HERE IS WHAT HAPPENS IN 1134 00:46:21,680 --> 00:46:24,400 THINGS LIKE SEA TURTLES TODAY 1135 00:46:24,400 --> 00:46:26,880 THIS WAS DISCOVERED BY KEN STORY 1136 00:46:26,880 --> 00:46:29,240 IN THE '70s, IF I REMEMBER 1137 00:46:29,240 --> 00:46:33,040 RIGHTLY. THEY DON'T HAVE A 1138 00:46:33,040 --> 00:46:34,880 SUCCINATE DEHYDROGENASE, THEY 1139 00:46:34,880 --> 00:46:37,160 HAVE A FUME RATE REDUCTASE. THE 1140 00:46:37,160 --> 00:46:39,120 FUME RATE KREBS CYCLE 1141 00:46:39,120 --> 00:46:40,280 INTERMEDIATE IS THE ELECTRON 1142 00:46:40,280 --> 00:46:42,800 ACCEPTOR SO TAKING FROM NADH 1143 00:46:42,800 --> 00:46:44,880 INTO THE RESPIRATORY CHAIN TO 1144 00:46:44,880 --> 00:46:46,320 MAKE ATP BUT INSTEAD OF GOING 1145 00:46:46,320 --> 00:46:47,880 THROUGH THE CHAIN TO OXYGEN IT 1146 00:46:47,880 --> 00:46:55,160 COMES TO FUME RATE. AND MAKES 1147 00:46:55,160 --> 00:46:56,720 SUCCINATE AS A WASTE PRODUCT. SO 1148 00:46:56,720 --> 00:46:59,080 KNOWN FOR DECADES. ONLY RECENTLY 1149 00:46:59,080 --> 00:47:01,640 MIKE MURPHY AN COLLEAGUES IN 1150 00:47:01,640 --> 00:47:03,240 CAMBRIDGE HAD A NATURE PAPER 1151 00:47:03,240 --> 00:47:05,600 NEARLY TEN YEARS AGO SHOWING 1152 00:47:05,600 --> 00:47:07,720 THAT IN REPROFUSION INJURY YOU 1153 00:47:07,720 --> 00:47:09,760 TEND TO ACCUMULATE SUCCINATE 1154 00:47:09,760 --> 00:47:10,440 THROUGH SOMETHING SIMILAR TO 1155 00:47:10,440 --> 00:47:12,800 THAT AND AS SOON AS YOU 1156 00:47:12,800 --> 00:47:15,280 REINTRODUCE OXYGEN YOU OXIDIZE 1157 00:47:15,280 --> 00:47:17,760 THAT SUCCINATE BACK TO FUME RATE 1158 00:47:17,760 --> 00:47:19,560 AND IT IS POWERING ELECTRON 1159 00:47:19,560 --> 00:47:21,480 TRANSFER BACK TO COMPLEX 1 SO A 1160 00:47:21,480 --> 00:47:24,720 HEART OF ISCHEMIA REPROFUSION 1161 00:47:24,720 --> 00:47:27,120 INJURY, I DUD MY Ph.D. ON AND 1162 00:47:27,120 --> 00:47:29,600 WISH I HAD MADE THAT DISCOVERY 1163 00:47:29,600 --> 00:47:31,800 BUT HE -- IT WAS 20 YEARS AFTER 1164 00:47:31,800 --> 00:47:33,440 WORKING ON THE SAME QUESTIONS 1165 00:47:33,440 --> 00:47:35,640 AND I WAS BEFUDDLED BY MY OWN 1166 00:47:35,640 --> 00:47:36,800 DATA WHICH POINTED STRAIGHT TO 1167 00:47:36,800 --> 00:47:42,000 THAT AND NEVER SAW IT. SO THIS 1168 00:47:42,000 --> 00:47:46,240 IS REALLY, COMPLEX 2 FUME RATE 1169 00:47:46,240 --> 00:47:47,840 REDUCTASE OR SUCCINATE 1170 00:47:47,840 --> 00:47:48,920 DEHYDROGENASE IS THE ONLY ENZYME 1171 00:47:48,920 --> 00:47:51,880 IN THE KREBS CYCLE THAT STILL IN 1172 00:47:51,880 --> 00:47:53,720 THE MEMBRANE AND IT IS GIVING 1173 00:47:53,720 --> 00:47:56,320 YOU EFFECTIVELY A READ OUT ON 1174 00:47:56,320 --> 00:47:58,000 HOW YOU ARE DOING WHAT IS THE 1175 00:47:58,000 --> 00:47:59,920 REDOX STATE OF THE MITOCHONDRIA 1176 00:47:59,920 --> 00:48:01,960 AS A WHOLE? THE REDOX STATE OF 1177 00:48:01,960 --> 00:48:03,840 THE CELL? HOW ARE YOU DOING? IN 1178 00:48:03,840 --> 00:48:06,960 A HYPOXIC SITUATION OR A 1179 00:48:06,960 --> 00:48:09,320 SITUATION WHICH A FALSE HYPOXIA? 1180 00:48:09,320 --> 00:48:12,360 ARE YOU DOING ALL RIGHT? IT 1181 00:48:12,360 --> 00:48:13,880 TELLS YOU A LOT ABOUT THE 1182 00:48:13,880 --> 00:48:15,440 ENVIRONMENT YOU ARE IN. SO 1183 00:48:15,440 --> 00:48:17,120 INTERESTING SUCCINATE IS A 1184 00:48:17,120 --> 00:48:20,800 REALLY POTENT EPIGENETIC SIGNAL 1185 00:48:20,800 --> 00:48:22,840 AND FUMARATE AS WELL. IF YOU 1186 00:48:22,840 --> 00:48:24,640 THINK IN THAT WAY HOW THE KREBS 1187 00:48:24,640 --> 00:48:26,680 CYCLE IS WORKING, THIS IS MY BAD 1188 00:48:26,680 --> 00:48:29,360 ATTEMPT TO DO A RESPIRATORY 1189 00:48:29,360 --> 00:48:31,560 CHAINS HERE COMPLEX 1, COMPLEX 1190 00:48:31,560 --> 00:48:34,320 2, COMPLEX 3 AND 4 AND ATP 1191 00:48:34,320 --> 00:48:35,280 SYNTHASE AND THE KREBS PSYCH 1192 00:48:35,280 --> 00:48:38,240 WILL THE MORE DETAIL MAKING NADH 1193 00:48:38,240 --> 00:48:41,320 WHICH GETS OXIDIZED IN COMPLEX 1194 00:48:41,320 --> 00:48:43,000 1. THAT IS WHAT ALL THE 1195 00:48:43,000 --> 00:48:45,840 TEXTBOOKS WILL SHOW. BUT NOW WE 1196 00:48:45,840 --> 00:48:48,320 IMAGINE THERE IS DAMAGE TO 1197 00:48:48,320 --> 00:48:50,240 COMPLEX 1. AND WHENEVER WE SEE 1198 00:48:50,240 --> 00:48:51,960 DAMAGE TO COMPLEX 1 WE TEND TO 1199 00:48:51,960 --> 00:48:55,200 THINK OKAY RESPIRATION IS GOING 1200 00:48:55,200 --> 00:48:57,320 TO BE IN SOME WAY, NOT GREAT FOR 1201 00:48:57,320 --> 00:48:59,280 RESPIRATION, IT IS NOT THAT BAD 1202 00:48:59,280 --> 00:49:00,600 NECESSARILY FOR PERSPIRATION, WE 1203 00:49:00,600 --> 00:49:03,160 CAN PUT ELECTRONS IN FROM VISUAL 1204 00:49:03,160 --> 00:49:04,640 3 PHOSPHATE FROM THE OUTSIDE 1205 00:49:04,640 --> 00:49:08,960 FROM THE CYTOSOL BY PHOSPHATE 1206 00:49:08,960 --> 00:49:10,640 DEHYDROGENASE STRAIGHT INTO 1207 00:49:10,640 --> 00:49:12,760 COMPLEX 3 SO ACTUALLY TERMS OF 1208 00:49:12,760 --> 00:49:14,880 ATP SYNTHESIS IT DOESN'T MATTER 1209 00:49:14,880 --> 00:49:16,920 MUCH IF COMPLEX 1 GOES DOWN, YOU 1210 00:49:16,920 --> 00:49:18,720 ARE OKAY FOR ENERGY AND A LOT OF 1211 00:49:18,720 --> 00:49:19,640 CANCER CELLS PROBABLY WORK THAT 1212 00:49:19,640 --> 00:49:21,760 WAY. IT DOES MARY FOR THE 1213 00:49:21,760 --> 00:49:26,280 OXIDATION OF NADH. THERE AREN'T 1214 00:49:26,280 --> 00:49:28,560 MANY OTHER SINKS FOR THE NADH SO 1215 00:49:28,560 --> 00:49:30,320 IT WILL BUILD UP AND YOU CAN 1216 00:49:30,320 --> 00:49:34,160 SHOW USING SURFACE THAT IT 1217 00:49:34,160 --> 00:49:36,320 BUILDS UP. IF IT IS BUILDING UP 1218 00:49:36,320 --> 00:49:38,840 IT WILL PUSH THE KREBS CYCLE IN 1219 00:49:38,840 --> 00:49:41,680 REVERSE. WHAT WE HAVE IS 1220 00:49:41,680 --> 00:49:43,520 ESPECIALLY SUCCINATE AND 1221 00:49:43,520 --> 00:49:45,280 CITRATE, THE LAST STEP FROM 1222 00:49:45,280 --> 00:49:48,440 CITRATE TO CITRATE TO ALPHA KETO 1223 00:49:48,440 --> 00:49:51,480 GLUTERATE THROUGH TO CITRATE, IS 1224 00:49:51,480 --> 00:49:52,840 COMMON IN CANCER, DRIVING PARTS 1225 00:49:52,840 --> 00:49:55,200 OF THE KREBS CYCLE USUALLY NOT 1226 00:49:55,200 --> 00:49:56,960 THE WHOLE CYCLE BUT PARTS 1227 00:49:56,960 --> 00:50:00,080 BACKWARDS. SO CITRATE AND 1228 00:50:00,080 --> 00:50:03,320 SUCCINATE WILL DISPERSE FROM THE 1229 00:50:03,320 --> 00:50:04,920 MITOCHONDRIA. SO WE HAVE A 1230 00:50:04,920 --> 00:50:06,520 PARTIAL REVERSAL OF THE KREBS 1231 00:50:06,520 --> 00:50:09,720 CYCLE, WHAT IS HAPPENING THERE, 1232 00:50:09,720 --> 00:50:10,920 ACETATE NOT GOING TO TALK ABOUT 1233 00:50:10,920 --> 00:50:13,480 THAT BUT THAT IS CENTRAL TO ALL 1234 00:50:13,480 --> 00:50:17,240 METABOLISM AND ACETYLCOA HISTONE 1235 00:50:17,240 --> 00:50:19,040 ACETYLATION, WE ARE DRIVING 1236 00:50:19,040 --> 00:50:22,440 GROWTH AXIS HERE. SIMILARLY FOR 1237 00:50:22,440 --> 00:50:26,120 SUCCINATE, THAT IS BOUNDING TO 1238 00:50:26,120 --> 00:50:29,160 PROLINE HYDROXYLASE, HIF 1 AL PA 1239 00:50:29,160 --> 00:50:31,840 IS ACTIVATED. SO DAMAGE TO 1240 00:50:31,840 --> 00:50:35,200 COMPLEX 1 IS GOING TO FLUX 1241 00:50:35,200 --> 00:50:36,680 THROUGH THE KREBS CYCLE WHICH 1242 00:50:36,680 --> 00:50:38,120 WILL GIVE A FALSE SIGNAL TO SAY 1243 00:50:38,120 --> 00:50:40,640 YOU ARE IN A HYPOXIC SITUATION 1244 00:50:40,640 --> 00:50:43,720 AND THE EPIGENETIC SIGNAL FROM 1245 00:50:43,720 --> 00:50:45,760 THAT IS GROW. THAT'S EXACTLY 1246 00:50:45,760 --> 00:50:49,040 WHAT CANCER CELLS WANT TO HEAR. 1247 00:50:49,040 --> 00:50:51,160 IT IS ALL COMING FROM THE SIMPLE 1248 00:50:51,160 --> 00:50:53,160 MECHANICS OF HOW THE ELECTRICAL 1249 00:50:53,160 --> 00:50:54,400 MEMBRANE POTENTIAL IS 1250 00:50:54,400 --> 00:50:55,920 INTERACTING WITH THE KREBS CYCLE 1251 00:50:55,920 --> 00:50:58,160 AND POTENTIAL FOR REVERSAL TO 1252 00:50:58,160 --> 00:51:00,000 THE KREBS CYCLE WHICH CAME AS A 1253 00:51:00,000 --> 00:51:01,240 SHOCK IN THE CANCER FIELD TEN 1254 00:51:01,240 --> 00:51:02,360 YEARS AGO WHEN THIS KIND OF 1255 00:51:02,360 --> 00:51:03,880 THING WAS FIRST DISCOVERED IT 1256 00:51:03,880 --> 00:51:05,520 WAS A SHOCK FOR THE KREBS CYCLE 1257 00:51:05,520 --> 00:51:07,120 BEING INVOLVED IN CANCER. WHEN 1258 00:51:07,120 --> 00:51:08,880 WE TAKE A FEW STEP BACKS AND 1259 00:51:08,880 --> 00:51:10,800 THINK, IT MAKES PERFECT SENSE 1260 00:51:10,800 --> 00:51:14,520 THAT IT'S CENTRAL TO AXIS. SO IT 1261 00:51:14,520 --> 00:51:16,840 IS NOT BY NO MEANS SAYING THIS 1262 00:51:16,840 --> 00:51:18,360 IS DRIVING CANCER, IT IS 1263 00:51:18,360 --> 00:51:21,000 PROVIDING I WOULD SAY A 1264 00:51:21,000 --> 00:51:22,680 PERMISSIVE ENVIRONMENT THAT 1265 00:51:22,680 --> 00:51:24,000 CANCER CELLS CAN TAKE ADVANTAGE 1266 00:51:24,000 --> 00:51:26,120 OF. WE ARE NOT A MILLION MILES 1267 00:51:26,120 --> 00:51:28,400 FROM THE WARBURG EFFECT WHICH IS 1268 00:51:28,400 --> 00:51:30,000 PROBABLY ONE OF THE THINGS THAT 1269 00:51:30,000 --> 00:51:31,640 MEANS THE MOST THING TO THE 1270 00:51:31,640 --> 00:51:32,800 LARGEST NUMBER OF PEOPLE, I 1271 00:51:32,800 --> 00:51:34,080 DON'T KNOW THAT ANY TWO PEOPLE 1272 00:51:34,080 --> 00:51:35,320 IN THIS ROOM WOULDN'T UNDERSTAND 1273 00:51:35,320 --> 00:51:37,160 EXACTLY THE SAME THING BY THE 1274 00:51:37,160 --> 00:51:39,640 WARBURG EFFEC EFFECT. BUT WHAT K 1275 00:51:39,640 --> 00:51:42,160 IT MEANS IS NOT REALLY WHAT 1276 00:51:42,160 --> 00:51:46,120 WARBURG HIMSELF MEANT BUT AS 1277 00:51:46,120 --> 00:51:50,200 TONY PUT IT IT IS BIOSYNTHETIC 1278 00:51:50,200 --> 00:51:51,200 MITOCHONDRIA, IT IS WORKING 1279 00:51:51,200 --> 00:51:54,800 LARGELY IN REVERSE LARGELY ABOUT 1280 00:51:54,800 --> 00:51:56,080 BIOSYNTHESIS AND LITTLE TO DO 1281 00:51:56,080 --> 00:51:58,760 WITH ATP AND IF WE THINK THAT 1282 00:51:58,760 --> 00:52:01,200 ANY OXIDATIVE ATP TO GROWS THAT 1283 00:52:01,200 --> 00:52:05,600 THE WRONG WAY, YOU NEED LOTS OF 1284 00:52:05,600 --> 00:52:07,080 NAPH, YOU NEED SOME ATP BUT NOT 1285 00:52:07,080 --> 00:52:08,880 TOO MUCH. YOU NEED PA MEMBRANE 1286 00:52:08,880 --> 00:52:10,240 POTENTIAL CERTAINLY BUT YOU CAN 1287 00:52:10,240 --> 00:52:11,880 MAINTAIN WITHOUT INVOLVING THE 1288 00:52:11,880 --> 00:52:14,040 KREBS CYCLE FROM THINGS LIKE 1289 00:52:14,040 --> 00:52:15,280 GLYCEROL PHOSPHATE. SO A 1290 00:52:15,280 --> 00:52:16,320 DIFFERENT WAY OF SEEING THIS 1291 00:52:16,320 --> 00:52:17,640 WIRING AND IF YOU THINK ABOUT IT 1292 00:52:17,640 --> 00:52:19,560 IN TERMS OF BIOSYNTHESIS YOU CAN 1293 00:52:19,560 --> 00:52:23,160 SEE WHY CANCER CELLS SOME CANCER 1294 00:52:23,160 --> 00:52:24,160 CELLS WOULD GRAB ON TO THAT FORM 1295 00:52:24,160 --> 00:52:32,240 OF WIRING. THIS IS THE -- NO, 1296 00:52:32,240 --> 00:52:35,240 OKAY. SO I SUSPECT THAT AS WE 1297 00:52:35,240 --> 00:52:39,800 GET OLDER, WE END UP WITH THE 1298 00:52:39,800 --> 00:52:41,040 SLIDE I SHOWED YOU WE END WITH 1299 00:52:41,040 --> 00:52:42,160 KREBS CYCLE WHICH IS SLOWING 1300 00:52:42,160 --> 00:52:43,520 DOWN, BEGINNING TO GO INTO 1301 00:52:43,520 --> 00:52:45,640 REVERSE WHICH IS BEGINNING TO 1302 00:52:45,640 --> 00:52:48,640 HAVE ACCUMULATION OF THINGS LIKE 1303 00:52:48,640 --> 00:52:51,480 CITRATE AND SUCCINATE. WHICH IS 1304 00:52:51,480 --> 00:52:53,120 TENDING TO MAKE US PUT ON WEIGHT 1305 00:52:53,120 --> 00:52:56,360 AS WE GET OLDER AND SLIGHTLY 1306 00:52:56,360 --> 00:52:58,200 LOWER OUR ENERGY LEVELS, STRIKES 1307 00:52:58,200 --> 00:52:59,960 ME NOT A MILLION MILE ACE WAY 1308 00:52:59,960 --> 00:53:03,240 FROM HOW I FEEL, IN MY MID 1309 00:53:03,240 --> 00:53:05,400 50s. AND I SUSPECT THAT IS A 1310 00:53:05,400 --> 00:53:06,400 PERMISSIVE ENVIRONMENT FOR 1311 00:53:06,400 --> 00:53:07,800 CANCER CELLS MUTATIONS AND SO ON 1312 00:53:07,800 --> 00:53:10,360 TO NAIL THAT METABOLISM IN AND 1313 00:53:10,360 --> 00:53:12,640 MAKE IT GO FORWARD. BUT NOT 1314 00:53:12,640 --> 00:53:14,320 EVERYTHING CAN ADAPT IN THAT 1315 00:53:14,320 --> 00:53:18,280 WAWAY. SOME CELLS ARE STUCK WITA 1316 00:53:18,280 --> 00:53:20,880 PARTICULAR SUBSTRATE. AND CANCER 1317 00:53:20,880 --> 00:53:22,680 CELLS LOVE GLUTAMINE AND IT WILL 1318 00:53:22,680 --> 00:53:24,920 DRIVE THE REVERSE KREBS CYCLE 1319 00:53:24,920 --> 00:53:29,240 WELL. BUT THE BETA CELLS WELL, 1320 00:53:29,240 --> 00:53:31,280 THEY ARE DETECTING GLUCOSE 1321 00:53:31,280 --> 00:53:33,400 LEVELS. I IMAGINE SOME PEOPLE 1322 00:53:33,400 --> 00:53:34,760 CAN TELL ME WHERE I GO WRONG 1323 00:53:34,760 --> 00:53:37,800 WITH THIS BUT MY UNDERSTANDING 1324 00:53:37,800 --> 00:53:40,680 IS THAT THE WAY THEY DETECT 1325 00:53:40,680 --> 00:53:42,880 GLUCOSE LEVELS IS BY MEMBRANE 1326 00:53:42,880 --> 00:53:44,600 POTENTIAL, THE ACTUAL SECRETION 1327 00:53:44,600 --> 00:53:47,640 OF INSULIN DEPENDS ON 1328 00:53:47,640 --> 00:53:48,840 MITOCHONDRIAL MEMBRANE 1329 00:53:48,840 --> 00:53:50,320 POTENTIAL. DON'T KNOW THERE IS 1330 00:53:50,320 --> 00:53:51,600 LARGE AM OF WORK ON THIS SO 1331 00:53:51,600 --> 00:53:52,760 INTERESTING TO HEAR FROM YOU 1332 00:53:52,760 --> 00:53:54,280 ABOUT THIS. BUT LET'S PRETEND IT 1333 00:53:54,280 --> 00:53:55,200 IS TRUE BECAUSE IT WOULD BE 1334 00:53:55,200 --> 00:53:59,280 INTERESTING IF IT WAS, WE HAVE 1335 00:53:59,280 --> 00:54:01,440 AN INCREASE IN GLUCOSE, IT GOES 1336 00:54:01,440 --> 00:54:03,120 STRAIGHT INTO THE MITOCHONDRIA, 1337 00:54:03,120 --> 00:54:05,640 THAT RAMPS UP KREBS CYCLE, THAT 1338 00:54:05,640 --> 00:54:08,960 RAMPS UP MEMBRANE POTENTIAL, 1339 00:54:08,960 --> 00:54:10,800 THAT LEADS TO RELEASE OF 1340 00:54:10,800 --> 00:54:13,080 SECRETION OF INSULIN. IF WE HAVE 1341 00:54:13,080 --> 00:54:15,720 DAMAGE TO THE RESPIRATORY CHAIN, 1342 00:54:15,720 --> 00:54:17,760 WHATEVER THAT DAMAGE MAYBE 1343 00:54:17,760 --> 00:54:20,640 CAUSED BY THEN THE GLUCOSE 1344 00:54:20,640 --> 00:54:22,480 DOESN'T -- MAY GET MANY THE SAME 1345 00:54:22,480 --> 00:54:24,080 WAY BUT IF THIS DAMAGE TO 1346 00:54:24,080 --> 00:54:25,600 COMPLEX 1 WE WON'T GENERATE 1347 00:54:25,600 --> 00:54:26,480 MEMBRANE POTENTIAL IN THE SAME 1348 00:54:26,480 --> 00:54:28,920 WAY. THEREFORE WE ARE NOT GOING 1349 00:54:28,920 --> 00:54:30,960 TO BE SECRETING INSULIN OR GOING 1350 00:54:30,960 --> 00:54:33,120 TO START SEEING ALL KINDS OF 1351 00:54:33,120 --> 00:54:36,320 PROBLEMS WITH DIABETES. MAYBE, 1352 00:54:36,320 --> 00:54:38,920 MAYBE NOT. THAT IS NOT MY MAIN 1353 00:54:38,920 --> 00:54:42,000 POINT, MY MAIN POINT IS WHY DO 1354 00:54:42,000 --> 00:54:46,480 NEURONS LOVE GLUCOSE? BECAUSE 1355 00:54:46,480 --> 00:54:49,360 MAYBE THEY ARE SIMILAR. MAYBE 1356 00:54:49,360 --> 00:54:50,360 THERE'S SOMETHING ABOUT RAMPING 1357 00:54:50,360 --> 00:54:52,560 UP MEMBRANE MANY POTENTIAL IN 1358 00:54:52,560 --> 00:54:55,440 GLUCOSE OR COULD BE LACTATE BUT 1359 00:54:55,440 --> 00:54:56,720 BASICALLY THE FORWARD KREBS 1360 00:54:56,720 --> 00:54:58,080 CYCLE AS WE KNOW IT, THAT IS 1361 00:54:58,080 --> 00:55:00,240 WHAT THEY WAN, THEY CAN WORK 1362 00:55:00,240 --> 00:55:02,680 FROM AS MATERIAL COA FROM 1363 00:55:02,680 --> 00:55:05,000 KETONES FINAL LACTATE, WORK FROM 1364 00:55:05,000 --> 00:55:09,120 GLUCOSE BUT ALL ARE COMPLEX SUB 1365 00:55:09,120 --> 00:55:10,320 INVESTIGATES THAT GO STRAIGHT 1366 00:55:10,320 --> 00:55:13,760 IN. THIS IS WORK THAT IS COMING 1367 00:55:13,760 --> 00:55:21,200 REALLY FROM ESTEL GOMEZ AND ERIC 1368 00:55:21,200 --> 00:55:22,240 SHOWN, I DON'T KNOW HOW WIDELY 1369 00:55:22,240 --> 00:55:23,760 ACCEPTED THIS IS BUT IT MAKES 1370 00:55:23,760 --> 00:55:25,880 SENSE TO ME. THEY ARE TALKING 1371 00:55:25,880 --> 00:55:27,560 THE MITOCHONDRIA ASSOCIATED 1372 00:55:27,560 --> 00:55:28,800 MEMBRANES WHICH IS THE PART OF 1373 00:55:28,800 --> 00:55:31,760 THE ENDOPLASMIC RETICULUM 1374 00:55:31,760 --> 00:55:33,920 SYNAPSING WITH MYCHON DRYIA AND 1375 00:55:33,920 --> 00:55:35,400 PROCESSING OF THINGS LIKE 1376 00:55:35,400 --> 00:55:38,520 AMYLOID PRECURSOR PROTEIN, AND 1377 00:55:38,520 --> 00:55:39,520 ALL KINDS OF OTHER THINGS ARE 1378 00:55:39,520 --> 00:55:42,160 HAPPENING I UNDERSTAND IN THE 1379 00:55:42,160 --> 00:55:43,320 MITOCHONDRIA ASSOCIATED 1380 00:55:43,320 --> 00:55:45,360 MEMBRANES. THEY ARE PUTTING 1381 00:55:45,360 --> 00:55:48,000 CALCIUM INTO THE MITOCHONDRIA. 1382 00:55:48,000 --> 00:55:50,360 AND WE HAVE THIS SAME SITUATION, 1383 00:55:50,360 --> 00:55:53,160 SOON AS CAPILLARIES OPEN UP, 1384 00:55:53,160 --> 00:55:58,640 GLUCOSE MOVES IN TO CELLS THE 1385 00:55:58,640 --> 00:56:01,840 CALCIUM MOVES IN, PYRUVATE 1386 00:56:01,840 --> 00:56:03,520 DEHYDROGENASE RAMPED UP, KREBS 1387 00:56:03,520 --> 00:56:05,440 CYCLE SPINS, WE HAVE A MEMBRANE 1388 00:56:05,440 --> 00:56:07,280 POTENTIAL SO WE HAVE A SUDDEN 1389 00:56:07,280 --> 00:56:08,640 INCREASE IN MEMBRANE POTENTIAL. 1390 00:56:08,640 --> 00:56:11,000 I WON'T TALK ABOUT THIS NOW BUT 1391 00:56:11,000 --> 00:56:13,560 I SUSPECT THAT IS GENERATING 1392 00:56:13,560 --> 00:56:15,000 ELECTROMAGNETIC FIELDS WHICH 1393 00:56:15,000 --> 00:56:16,720 WILL DO SIGNALING BUT WE WON'T 1394 00:56:16,720 --> 00:56:18,400 TALK ABOUT THAT SO MUCH AS WE 1395 00:56:18,400 --> 00:56:19,840 HAVE THE SAME PROBLEM AS IF 1396 00:56:19,840 --> 00:56:25,960 THERE IS DAMAGE TO COMPLEX 1, 1397 00:56:25,960 --> 00:56:26,920 THEN WE CAN'T BOOT UP THE SYSTEM 1398 00:56:26,920 --> 00:56:30,560 IN THE SAME WAY. WE STILL WE ARE 1399 00:56:30,560 --> 00:56:32,880 RELIANT ON ONE SUBSTRATE GLUCOSE 1400 00:56:32,880 --> 00:56:34,600 DAMAGE TO COMPLEX 1 MEANS NO 1401 00:56:34,600 --> 00:56:36,040 INCREASING MEMBRANE POTENTIAL 1402 00:56:36,040 --> 00:56:38,320 AND WE POTENTIALLY ARE GOING TO 1403 00:56:38,320 --> 00:56:42,080 BECOME VULNERABLE TO ALZHEIMER'S 1404 00:56:42,080 --> 00:56:43,720 DISEASE. ONE WAY OUT OF THAT IS 1405 00:56:43,720 --> 00:56:47,040 TO PUMP MORE CALCIUM IN. TO TRY 1406 00:56:47,040 --> 00:56:48,520 AND GET MORE BANG FOR YOUR BUCK 1407 00:56:48,520 --> 00:56:50,320 IF YOU LIKE AND JUST INCREASE 1408 00:56:50,320 --> 00:56:53,840 THE CALCIUM LEVELS, INCREASE THE 1409 00:56:53,840 --> 00:56:55,920 ACTIVATION OF PYRUVATE 1410 00:56:55,920 --> 00:56:57,480 DEHYDROGENASE AND PUMP UP 1411 00:56:57,480 --> 00:57:02,960 MEMBRANE POTENTIAL THAT WAY 1412 00:57:02,960 --> 00:57:04,760 WAY.ERRATIC SHOWN AND GOMEZ 1413 00:57:04,760 --> 00:57:07,440 THEIR ARGUMENT ISN'T THAT HIGH 1414 00:57:07,440 --> 00:57:10,640 PER TROPHY WITH MITOCHONDRIA 1415 00:57:10,640 --> 00:57:13,120 ASSOCIATED MEMBRANES IF IT IS 1416 00:57:13,120 --> 00:57:14,280 DRIVING ALZHEIMER'S DISEASE SO 1417 00:57:14,280 --> 00:57:16,680 IN THE A PROBLEM WITH 1418 00:57:16,680 --> 00:57:17,960 MITOCHONDRIA DIRECTLY SO MUCH 1419 00:57:17,960 --> 00:57:20,000 PROBLEM WITH OVERACCUMULATION OF 1420 00:57:20,000 --> 00:57:23,040 CALCIUM IN THE ENDO E PALACE MIC 1421 00:57:23,040 --> 00:57:25,120 RETICULUM SURROUNDING THE 1422 00:57:25,120 --> 00:57:27,760 MITOCHONDRIA. YOU TELL ME, BUT 1423 00:57:27,760 --> 00:57:30,360 IT LINKS IN NICELY AND WHETHER 1424 00:57:30,360 --> 00:57:32,600 RIGHT OR WRONG, THESE THINGS 1425 00:57:32,600 --> 00:57:35,280 SEEM TO BE VERY CLOSELY LINKED 1426 00:57:35,280 --> 00:57:36,400 NOT ONLY TO CANCER AS I 1427 00:57:36,400 --> 00:57:40,040 SUGGESTED OR TO DIABETES BUT 1428 00:57:40,040 --> 00:57:41,280 ALSO NEURODEGENERATIVE 1429 00:57:41,280 --> 00:57:42,440 CONDITIONS LIKE ALZHEIMER'S. 1430 00:57:42,440 --> 00:57:44,040 I'M USING THE SAME DIAGRAMS THAT 1431 00:57:44,040 --> 00:57:46,880 I WAS FOR THE ORIGIN OF LIFE. 1432 00:57:46,880 --> 00:57:48,720 BASICALLY NO CHANGE THERE. SO IT 1433 00:57:48,720 --> 00:57:50,240 IS NOT THAT I'M TELLING YOU THIS 1434 00:57:50,240 --> 00:57:51,320 IS RIGHT OR WRONG, TELLING YOU 1435 00:57:51,320 --> 00:57:54,320 HERE IS HOW WE SEE IT, MAY I 1436 00:57:54,320 --> 00:57:56,240 HOPE GIVE YOU SOME IMPULSE TO 1437 00:57:56,240 --> 00:58:01,080 THINK ABOUT THESE QUESTIONS. I 1438 00:58:01,080 --> 00:58:03,760 THINK I DON'T NEED TO CLOSE 1439 00:58:03,760 --> 00:58:06,000 PROPERLY, ELECTRIC MEMBRANES 1440 00:58:06,000 --> 00:58:08,680 DRIVE CO 2 FIXATION, METABOLISM 1441 00:58:08,680 --> 00:58:10,800 SPONTANEOUS, GENES AMPLIFY THIS 1442 00:58:10,800 --> 00:58:14,160 METABOLIC NETWORK. THAT MEANS 1443 00:58:14,160 --> 00:58:15,840 METABOLISM GIVES MEANING TO 1444 00:58:15,840 --> 00:58:16,440 GENETIC INFORMATION UNDISTILLED 1445 00:58:16,440 --> 00:58:19,400 DOES. RESPIRATION IS -- AND 1446 00:58:19,400 --> 00:58:21,520 STILL DOES. AND DAMAGE TO 1447 00:58:21,520 --> 00:58:23,480 RESERVATION WHICH ACCUMULATES IN 1448 00:58:23,480 --> 00:58:29,680 ALL OF US -- RESPIRATION LEADING 1449 00:58:29,680 --> 00:58:32,000 TO EPIGENETIC SHIFT IN ADDITION 1450 00:58:32,000 --> 00:58:35,440 TO WHAT IS GOING WRONG WITH 1451 00:58:35,440 --> 00:58:37,160 AGING. I WANT TO CALL ATTENTION 1452 00:58:37,160 --> 00:58:39,120 TO MY LAB. THE SPY GOODBYES IN 1453 00:58:39,120 --> 00:58:40,760 THE MIDDLE, SOME ARE STILL IN 1454 00:58:40,760 --> 00:58:43,200 THE LAB, SOME HAVE LEFT. THIS IS 1455 00:58:43,200 --> 00:58:45,640 A BIRTHDAY PRESENT, THEY ARE 1456 00:58:45,640 --> 00:58:48,240 HOLDING A KREBS CYCLE, I LOVE 1457 00:58:48,240 --> 00:58:50,480 THAT SO MUCH, AID TO PUT THE 1458 00:58:50,480 --> 00:58:51,400 NEWER MEMBERS OF THE LAB AROUND 1459 00:58:51,400 --> 00:58:53,680 THE EDGE. BUT THEY ARE BRAVE 1460 00:58:53,680 --> 00:58:55,040 PEOPLE TO BECOME ASSOCIATED 1461 00:58:55,040 --> 00:58:55,920 SEARCH WARRANT WITH SOMEONE LIKE 1462 00:58:55,920 --> 00:58:58,440 ME AND WORK ON QUESTIONS LIKE 1463 00:58:58,440 --> 00:59:00,440 THE ORIGIN OF LIFE, THEY HAVE 1464 00:59:00,440 --> 00:59:01,720 BEEN DOING BEAUTIFUL SCIENCE, 1465 00:59:01,720 --> 00:59:03,120 THE WORK ON ORIGIN OF LIFE IS 1466 00:59:03,120 --> 00:59:04,840 ENTIRELY DOWN TO THEM AND I FIND 1467 00:59:04,840 --> 00:59:06,680 IT INSPIRING TO BE WORKING WITH 1468 00:59:06,680 --> 00:59:09,680 THEM EVERY DAY. SO THANK YOU TO 1469 00:59:09,680 --> 00:59:10,800 THEM AND THE FUNDERS AND THANK 1470 00:59:10,800 --> 00:59:11,760 YOU FOR LISTENING. 1471 00:59:11,760 --> 00:59:18,200 [APPLAUSE] 1472 00:59:18,200 --> 00:59:20,640 >> THANK YOU, NICK, FOR THIS 1473 00:59:20,640 --> 00:59:22,760 REALLY VERY EXCITING PROVOCATIVE 1474 00:59:22,760 --> 00:59:25,520 TALK. WE HAVE A SERIES OF 1475 00:59:25,520 --> 00:59:26,960 QUESTIONS. 1476 00:59:26,960 --> 00:59:29,000 >> SO I THINK IT IS VERY 1477 00:59:29,000 --> 00:59:30,560 INTERESTING WHAT YOU TOLD US 1478 00:59:30,560 --> 00:59:32,200 TODAY AND AS FAR AS I UNDERSTOOD 1479 00:59:32,200 --> 00:59:34,720 BASICALLY THE MAIN IDEA IS THAT 1480 00:59:34,720 --> 00:59:37,520 FIRST CHEMISTRY THEN THERE WERE 1481 00:59:37,520 --> 00:59:38,400 GENES THAT WERE PRODUCING 1482 00:59:38,400 --> 00:59:40,840 PROTEINS THAT MADE THE CHEMISTRY 1483 00:59:40,840 --> 00:59:43,920 THE MOST EFFICIENT IN THIS 1484 00:59:43,920 --> 00:59:45,560 PARTICULAR ENVIRONMENT FOR THE 1485 00:59:45,560 --> 00:59:47,000 UNICELLULAR ORGANISMS BUT THEN 1486 00:59:47,000 --> 00:59:49,120 FOR THE MULTI-CELLULAR ORGANISMS 1487 00:59:49,120 --> 00:59:50,280 BASICALLY WHAT THIS LAST PART 1488 00:59:50,280 --> 00:59:53,600 YOU SHOWED THAT ALL DIFFERENT 1489 00:59:53,600 --> 00:59:55,440 TISSUES LIKE HAVE DIFFERENT 1490 00:59:55,440 --> 00:59:57,040 CHEMISTRY ENVIRONMENTS 1491 00:59:57,040 --> 00:59:58,000 BASICALLY, WAS THIS RELATED TO 1492 00:59:58,000 --> 01:00:02,200 THE FUNCTIONING ORION LIKE SOME 1493 01:00:02,200 --> 01:00:04,840 PROCESS CANCER AGING AND SO 1494 01:00:04,840 --> 01:00:08,360 FORTH. SO THE BASICALLY 1495 01:00:08,360 --> 01:00:09,640 DIFFERENT CELLS IN THE ORGANISM 1496 01:00:09,640 --> 01:00:11,560 THEY HAVE THE SAME GENES BECAUSE 1497 01:00:11,560 --> 01:00:14,000 THEY COME FROM THE SAME GENOME 1498 01:00:14,000 --> 01:00:15,880 SO THEY CAN GET STUCK WITH SAME 1499 01:00:15,880 --> 01:00:18,200 GENES THAT HAVE TO WORK IN 1500 01:00:18,200 --> 01:00:19,680 DIFFERENT ENVIRONMENTS, 1501 01:00:19,680 --> 01:00:23,640 MULTI-CELLULAR ORGANISMS, THEY 1502 01:00:23,640 --> 01:00:25,080 THINK ANY EVIDENCE 1503 01:00:25,080 --> 01:00:25,880 MULTI-CELLULAR ORGANISM THERE IS 1504 01:00:25,880 --> 01:00:29,880 IS MORE REGULATION IN TERMS OF 1505 01:00:29,880 --> 01:00:30,800 GENE EXPRESSION OR SOMETHING 1506 01:00:30,800 --> 01:00:32,440 LIKE THIS TO MAKE SURE THAT ALL 1507 01:00:32,440 --> 01:00:35,240 THE DIFFERENT CELLS IN THE SAME 1508 01:00:35,240 --> 01:00:36,520 ORGANISM FUNCTION IN DIFFERENT 1509 01:00:36,520 --> 01:00:38,520 CHEMICAL ENVIRONMENTS CAN STILL 1510 01:00:38,520 --> 01:00:41,280 FUNCTION AT THE MOST OPTIMALLY. 1511 01:00:41,280 --> 01:00:44,320 >> YES, I MEAN OBVIOUSLY THERE 1512 01:00:44,320 --> 01:00:46,800 IS A HUGE REQUIREMENT FOR GENE 1513 01:00:46,800 --> 01:00:48,480 REMEMBER RATION AND SO ON. AND I 1514 01:00:48,480 --> 01:00:51,720 THINK THAT IS WHAT BIOMEDICAL 1515 01:00:51,720 --> 01:00:53,720 SCIENCES OVER THE LAST FEW 1516 01:00:53,720 --> 01:00:57,720 DECADES HAS BEEN STUDYING TO A 1517 01:00:57,720 --> 01:01:00,400 LARGE EXTENT. OF COURSE, IT IS A 1518 01:01:00,400 --> 01:01:03,280 VITAL IMPORTANCE TO HOW THINGS 1519 01:01:03,280 --> 01:01:05,720 WORK. BUT I THINK THIS MAYBE A 1520 01:01:05,720 --> 01:01:06,920 BLIND SPOT FOR SOME OF THE MORE 1521 01:01:06,920 --> 01:01:09,440 OBVIOUS THINGS THAT UNDERPIN IN 1522 01:01:09,440 --> 01:01:12,000 PART BECAUSE THEY -- THEY SEE 1523 01:01:12,000 --> 01:01:14,720 THE DUSTY TEXTBOOK BIOCHEMISTRY, 1524 01:01:14,720 --> 01:01:17,080 THE IDEA THE KREB CYCLE IS THE 1525 01:01:17,080 --> 01:01:19,640 CENTER OF METABOLISM IN THE CELL 1526 01:01:19,640 --> 01:01:21,200 Z IN SOME SENSE EVERYBODY KNOWS 1527 01:01:21,200 --> 01:01:23,080 THAT AND SOME OTHER SENSE NOT 1528 01:01:23,080 --> 01:01:24,520 ACTUALLY SO OBVIOUS AS YOU MIGHT 1529 01:01:24,520 --> 01:01:25,520 THINK BECAUSE OF THE 1530 01:01:25,520 --> 01:01:27,520 PARTITIONING OF CELLS, BETWEEN 1531 01:01:27,520 --> 01:01:29,040 DIFFERENT ORGANELLES AND SO ON 1532 01:01:29,040 --> 01:01:34,560 SO IT IS -- AND I THINK OLD 1533 01:01:34,560 --> 01:01:36,440 IDEAINGS LIKE KREBS PSYCH 1534 01:01:36,440 --> 01:01:37,000 MILLION BIOLOGY TEND TO BE 1535 01:01:37,000 --> 01:01:39,240 FORGOTTEN BECAUSE THEY ARE OLD. 1536 01:01:39,240 --> 01:01:40,880 AND IT TAKES A WHILE FOR PEOPLE 1537 01:01:40,880 --> 01:01:44,880 TO SEE IT WITH FRESH EYES SO I 1538 01:01:44,880 --> 01:01:46,560 THINK A CHANGE THAT HAPPENED IS 1539 01:01:46,560 --> 01:01:49,360 REGULATION IS LARGELY ABOUT 1540 01:01:49,360 --> 01:01:52,200 LARGELY IS TOO STRONG A WORD BUT 1541 01:01:52,200 --> 01:01:55,080 ABOUT MAKING SURE THAT OF THE 1542 01:01:55,080 --> 01:01:56,680 KIND OF MAINTAINIOUS FLUXES MOST 1543 01:01:56,680 --> 01:01:58,400 LIKELY TO HAPPEN THE FORMS YOU 1544 01:01:58,400 --> 01:02:00,560 DON'T WANT DON'T HAPPEN IN THIS 1545 01:02:00,560 --> 01:02:02,240 PLACE. SO AS WE SEE REGULATION 1546 01:02:02,240 --> 01:02:05,280 BREAKING DOWN WHAT YOU SEE IS A 1547 01:02:05,280 --> 01:02:08,200 REASSERTION OF SPONTANEOUS 1548 01:02:08,200 --> 01:02:09,320 METABOLISM THERE FROM THE VERY 1549 01:02:09,320 --> 01:02:10,880 BEGINNING WHICH HAS A TENDENCY 1550 01:02:10,880 --> 01:02:12,280 TO DO CERTAIN THINGS, THE THINGS 1551 01:02:12,280 --> 01:02:14,400 IT DOES WILL DEPEND ON AGAIN 1552 01:02:14,400 --> 01:02:15,960 ANOTHER OLD FASHIONED ASPECT OF 1553 01:02:15,960 --> 01:02:18,200 SCIENCE WHICH IS WHAT IS THE 1554 01:02:18,200 --> 01:02:21,400 NADH TO NAD RATIO? WHAT IS 1555 01:02:21,400 --> 01:02:25,480 ACETYLCO TO COA RATIO? VARIOUS 1556 01:02:25,480 --> 01:02:30,440 RATIOS ARCTP TO ADP RATIO. THEY 1557 01:02:30,440 --> 01:02:31,560 ARE GIVING A GROUND STATE OF THE 1558 01:02:31,560 --> 01:02:34,080 CELL AND IF YOU ARE LOOSING 1559 01:02:34,080 --> 01:02:35,880 REGULATORY CONTROL THE GROUND 1560 01:02:35,880 --> 01:02:37,320 STATE DRIVES THINGS AND 1561 01:02:37,320 --> 01:02:40,680 COMPENSATION IS EPIGENETIC 1562 01:02:40,680 --> 01:02:41,480 COMPENSATION, ABOUT WHICH PART 1563 01:02:41,480 --> 01:02:43,600 OF THE NUCLEUS IS CLOSED DOWN 1564 01:02:43,600 --> 01:02:46,000 AND WHICH BITS ARE UPREGULATED 1565 01:02:46,000 --> 01:02:48,600 SO ON. AND SUDDENLY IN A WAY 1566 01:02:48,600 --> 01:02:50,520 OUTSIDE THE DOMAIN OF REGULATION 1567 01:02:50,520 --> 01:02:53,040 AND INTO DOMAIN OF COMPENSATION 1568 01:02:53,040 --> 01:02:55,080 FOR A PROBLEM AND COMPENSATION 1569 01:02:55,080 --> 01:02:56,920 ON A FAIRLY GRANULAR SCALE 1570 01:02:56,920 --> 01:02:58,560 ACROSS THE NUCLEUS IS NOT ONE 1571 01:02:58,560 --> 01:03:01,480 PATHWAY OR DIFFERENT PATHWAY, IT 1572 01:03:01,480 --> 01:03:03,000 IS A STRESS RESPONSE TO ENTIRE 1573 01:03:03,000 --> 01:03:05,840 SYSTEM WHICH IS NOW OUT OF ORDER 1574 01:03:05,840 --> 01:03:07,480 OUT OF SYNC. SO IT IS NOT THAT 1575 01:03:07,480 --> 01:03:08,840 I'M TELLING YOU ANYTHING YOU 1576 01:03:08,840 --> 01:03:09,920 DON'T KNOW, IT IS JUST THAT I'M 1577 01:03:09,920 --> 01:03:11,520 TRYING TO GET YOU TO SEE IT 1578 01:03:11,520 --> 01:03:13,040 THROUGH SLIGHTLY FRESH EYES 1579 01:03:13,040 --> 01:03:20,080 BECAUSE IT IS UNDERNEATH THIS 1580 01:03:20,080 --> 01:03:20,600 BEAUTIFUL FINES REGULAR 1581 01:03:20,600 --> 01:03:21,640 REGULATION OF A SYSTEM IS DOING 1582 01:03:21,640 --> 01:03:24,400 REGARDLESS. FROM A TOP DOWN VIEW 1583 01:03:24,400 --> 01:03:25,760 WE THINK GENES INVENTED 1584 01:03:25,760 --> 01:03:27,440 METABOLISM AND THE REGULATION 1585 01:03:27,440 --> 01:03:29,440 CONTROLS FLUX. I WOULD SAY THE 1586 01:03:29,440 --> 01:03:31,520 OTHER WAY UP, METABOLISM 1587 01:03:31,520 --> 01:03:33,880 INVENTED GENE, AND YES GENES 1588 01:03:33,880 --> 01:03:35,440 CONTROL FLUX BUT THE FLUX CAN 1589 01:03:35,440 --> 01:03:36,480 REASSERT ITSELF IN INTERESTING 1590 01:03:36,480 --> 01:03:37,720 AND UNUSUAL WAYS. 1591 01:03:37,720 --> 01:03:39,400 >> THANK YOU, VERY INTERESTING. 1592 01:03:39,400 --> 01:03:42,400 >> LET ME REMINDER, THERE IS A 1593 01:03:42,400 --> 01:03:44,040 RECEPTION RIGHT AFTER THIS, SO 1594 01:03:44,040 --> 01:03:47,720 IF YOU HAVE MORE DETAILED 1595 01:03:47,720 --> 01:03:49,080 QUESTIONS, YOU WANT TO DISCUSS 1596 01:03:49,080 --> 01:03:52,760 AT LENGTH THAT IS THE PLACE. 1597 01:03:52,760 --> 01:03:54,360 MEANWHILE WE HAVE SEVERAL SHORT 1598 01:03:54,360 --> 01:03:54,640 QUESTIONS. 1599 01:03:54,640 --> 01:03:56,880 >> THANK YOU VERY MUCH. IS THIS 1600 01:03:56,880 --> 01:03:59,640 WORKING? 1601 01:03:59,640 --> 01:04:03,320 >> YES. 1602 01:04:03,320 --> 01:04:04,760 >> FANTASTIC, FANTASTIC 1603 01:04:04,760 --> 01:04:08,760 PRESENTATION. I'M (INAUDIBLE) 1604 01:04:08,760 --> 01:04:13,760 IMMUNOLOGIST WITH 40 YEARS OF 1605 01:04:13,760 --> 01:04:15,760 PROTEIN CHEMISTRY IMMUNOLOGY AND 1606 01:04:15,760 --> 01:04:20,320 CANCER AN VACCINE SCIENCES. 1607 01:04:20,320 --> 01:04:23,440 (INAUDIBLE) PROCESS AND A LOT OF 1608 01:04:23,440 --> 01:04:27,360 QUESTION, BUT MY PRINCIPLE 1609 01:04:27,360 --> 01:04:31,120 QUESTION IS, DO YOU THINK THAT 1610 01:04:31,120 --> 01:04:34,800 THE MYCHON DEAL FUNCTIONALITY 1611 01:04:34,800 --> 01:04:36,960 WHICH IS MITOCHONDRIAL 1612 01:04:36,960 --> 01:04:41,400 FUNCTIONALITY AFTER EXPOSURE OF 1613 01:04:41,400 --> 01:04:45,000 THE NEWBORN WOULD BE COMPLETED 1614 01:04:45,000 --> 01:04:49,600 ALONG WITH ORGAN GENESIS AND 1615 01:04:49,600 --> 01:04:55,720 ANGIOGENESIS, WHICH PART OF 1616 01:04:55,720 --> 01:05:01,000 MITOCHONDRIA MAY BILL NOT 1617 01:05:01,000 --> 01:05:01,400 FUNCTIONAL AND. 1618 01:05:01,400 --> 01:05:08,400 THE EXPOSURE TO OXYGEN HAPPENS 1619 01:05:08,400 --> 01:05:11,400 IT TAKES STILL A FEW MONTHS FOR 1620 01:05:11,400 --> 01:05:15,480 THE MITOCHONDRIA TO BE FULLY 1621 01:05:15,480 --> 01:05:18,760 FUNCTIONAL BECAUSE THE NEWBORN 1622 01:05:18,760 --> 01:05:21,920 BABY IMMUNE SYSTEM IS DEPENDENT 1623 01:05:21,920 --> 01:05:25,160 STILL ON THE MOTHERS IMMUNITY. 1624 01:05:25,160 --> 01:05:27,800 AND ANOTHER MAYBE INTERESTING 1625 01:05:27,800 --> 01:05:32,120 THING IS WE HAVE COMPARED THE 1626 01:05:32,120 --> 01:05:36,400 GROWTH -- UNIGROWTH OF EMBRYO TO 1627 01:05:36,400 --> 01:05:36,800 THE CANCER -- 1628 01:05:36,800 --> 01:05:38,760 >> WE ARE RUNNING OUT OF TIME, 1629 01:05:38,760 --> 01:05:40,000 COULD YOU ASK YOUR QUESTION? 1630 01:05:40,000 --> 01:05:41,680 >> THAT IS WHAT I WAS ASKING. I 1631 01:05:41,680 --> 01:05:45,160 THINK HE HEARD ME. 1632 01:05:45,160 --> 01:05:47,120 >> SO INTERPLAY BETWEEN OXYGEN 1633 01:05:47,120 --> 01:05:49,000 AND THE IMMUNE SYSTEM AND 1634 01:05:49,000 --> 01:05:53,240 MITOCHONDRIA ESPECIALLY DURING 1635 01:05:53,240 --> 01:05:56,320 EARLY LIFE AND EMBRYONIC 1636 01:05:56,320 --> 01:05:59,040 DEVELOPMENT AND BIRTH. I THINK 1637 01:05:59,040 --> 01:06:00,400 IT IS BECOME INCREASINGLY CLEAR 1638 01:06:00,400 --> 01:06:02,960 THE LAST FEW YEARS MITOCHONDRIA 1639 01:06:02,960 --> 01:06:04,760 SENTRA TO THE INFLAMMASOME, I 1640 01:06:04,760 --> 01:06:06,000 DON'T THINK WE KNOW A GREAT DEAL 1641 01:06:06,000 --> 01:06:09,000 ABOUT IT BUT A LOT OF WORK WITH 1642 01:06:09,000 --> 01:06:12,840 COVID IN RECENT TIMES OBVIOUSLY 1643 01:06:12,840 --> 01:06:15,560 HAS SUGGESTED THAT THE 1644 01:06:15,560 --> 01:06:18,600 UPREGULATION OF ANNA BOWISM BY 1645 01:06:18,600 --> 01:06:19,880 CANCER CELLS IS WHAT VIRUSES 1646 01:06:19,880 --> 01:06:21,720 WANT AS WELL, I JUST VISITED 1647 01:06:21,720 --> 01:06:24,720 DOUG WALLACE IN PHILADELPHIA AND 1648 01:06:24,720 --> 01:06:27,320 HE IS WORKING A LOT. WHAT I 1649 01:06:27,320 --> 01:06:28,760 FOUND IS DOWN REGULATION OF 1650 01:06:28,760 --> 01:06:31,160 OXIDATIVE PHOSPHORYLATION, 1651 01:06:31,160 --> 01:06:32,800 UPREGULATION OF GLYCOLYSIS AND 1652 01:06:32,800 --> 01:06:35,920 REVERSE FLUX IN GENES SO HIF 1 1653 01:06:35,920 --> 01:06:39,400 ALPHA INVOLVED AND SO ON, AND 1654 01:06:39,400 --> 01:06:42,720 THE LOSS OF OXIDIZE 1655 01:06:42,720 --> 01:06:43,840 MITOCHONDRIAL DNA TO ACTIVATING 1656 01:06:43,840 --> 01:06:45,640 THE INFLAMMASOME SO THESE 1657 01:06:45,640 --> 01:06:47,600 PROCESSES ARE AGAIN CENTRAL AND 1658 01:06:47,600 --> 01:06:49,640 REALLY STRONGLY CONSERVED, IT IS 1659 01:06:49,640 --> 01:06:51,480 INTERESTING TO ME THAT THE 1660 01:06:51,480 --> 01:06:52,760 MITOCHONDRIA SEEM TO PLAY A 1661 01:06:52,760 --> 01:06:54,840 CRITICAL AND CENTRAL ROLE IN 1662 01:06:54,840 --> 01:06:55,680 IMMUNE ACTIVATION. 1663 01:06:55,680 --> 01:06:58,080 >> THANK YOU SO MUCH. 1664 01:06:58,080 --> 01:07:02,280 >> THANK YOU. 1665 01:07:02,280 --> 01:07:03,520 >> THANKS THAT WAS A BEAUTIFUL 1666 01:07:03,520 --> 01:07:03,760 TALK. 1667 01:07:03,760 --> 01:07:04,160 >> THANK YOU. 1668 01:07:04,160 --> 01:07:07,240 >> I MANY NAME IS DAVID L -- MY 1669 01:07:07,240 --> 01:07:13,880 NAME IS DAVID LEVIN BIOCHEMIST 1670 01:07:13,880 --> 01:07:16,280 IN UCI WHO USED TO FOLLOW THESE 1671 01:07:16,280 --> 01:07:17,520 THINGS CLOSELY. TWO SMALL 1672 01:07:17,520 --> 01:07:19,760 QUESTIONS. THE FIRST ONE, GIVEN 1673 01:07:19,760 --> 01:07:23,800 THAT YOU ARE SAYING LIFE BEGAN 1674 01:07:23,800 --> 01:07:28,760 ON EARTH AND OCEAN COOL OCEAN 1675 01:07:28,760 --> 01:07:32,520 AVENA I ASSUME, HOW DOES THAT 1676 01:07:32,520 --> 01:07:36,680 SPEAK TO THE NOTION OF PAN 1677 01:07:36,680 --> 01:07:39,600 SPERMIA AND IS THE UNIVERSE 1678 01:07:39,600 --> 01:07:40,920 TEAMING WITH LIFE? THAT'S 1679 01:07:40,920 --> 01:07:42,920 QUESTION ONE. 1680 01:07:42,920 --> 01:07:45,160 >> I WILL ANSWER QUESTION ONE 1681 01:07:45,160 --> 01:07:49,480 QUICKLY. I CAN'T DISPROVE PAN 1682 01:07:49,480 --> 01:07:50,920 SPERMIA BUT DON'T THINK IT IS A 1683 01:07:50,920 --> 01:07:52,720 HELPFUL HIGH POTSIES BECAUSE IT 1684 01:07:52,720 --> 01:07:54,040 PUSHES THE QUESTION TO SOMEWHERE 1685 01:07:54,040 --> 01:07:56,560 ELSELSE. MAY WELL BE LIFE WAS 1686 01:07:56,560 --> 01:07:57,480 SEEDED FROM SOMEWHERE ELSE IN 1687 01:07:57,480 --> 01:07:59,880 THE UNIVERSE, WHERE UNDER WHAT 1688 01:07:59,880 --> 01:08:02,240 CONDITIONS WHEN, HOW LONG DID IT 1689 01:08:02,240 --> 01:08:03,720 TAKE? IT CEASES TO BECOME 1690 01:08:03,720 --> 01:08:05,280 SCIENCE. I DON'T KNOW WHY IT IS 1691 01:08:05,280 --> 01:08:08,520 SO POPULAR BECAUSE IT DOESN'T -- 1692 01:08:08,520 --> 01:08:09,720 EVERYTHING I SAID MAYBE WRONG 1693 01:08:09,720 --> 01:08:12,280 BECAUSE IT IS UNDERPIND BY 1694 01:08:12,280 --> 01:08:13,960 ASSUMPTION THAT LIFE STARTED ON 1695 01:08:13,960 --> 01:08:15,160 EARTH WHICH MAYBE WRONG BUT WE 1696 01:08:15,160 --> 01:08:16,800 HAVE TO START SOMEWHERE. AND 1697 01:08:16,800 --> 01:08:18,600 SCIENCE IS UNDERPINNED BY AN 1698 01:08:18,600 --> 01:08:20,400 AIONAL WHICH IS THAT THE WORLD 1699 01:08:20,400 --> 01:08:24,200 IS EXPLICABLE BY NON-MIRACULOUS 1700 01:08:24,200 --> 01:08:26,320 FORCES AND LAWS OF NATURE DON'T 1701 01:08:26,320 --> 01:08:27,120 BROADLY CHANGE VERY MUCH OVER 1702 01:08:27,120 --> 01:08:29,600 TIME. AND THOSE ARE KIND OF 1703 01:08:29,600 --> 01:08:33,400 ASSUMPTIONS AS WELL, AND SO I 1704 01:08:33,400 --> 01:08:34,720 THINK HOPKINS RAISED THE IDEA 1705 01:08:34,720 --> 01:08:37,200 YOU CHOOSE THE SIMPLEST ANSWER 1706 01:08:37,200 --> 01:08:40,720 IS AGAIN AN ASSUMPTION, NOT 1707 01:08:40,720 --> 01:08:43,520 PROVED. SO I CAN'T SAY THAT PAN 1708 01:08:43,520 --> 01:08:45,640 SPERMIA DIDN'T HAPPEN AN LIFE 1709 01:08:45,640 --> 01:08:47,120 WASN'T SEEDED FROM SOMEWHERE 1710 01:08:47,120 --> 01:08:48,480 ELSE BUT THAT MEANS NO POINT 1711 01:08:48,480 --> 01:08:49,720 DOING ANYTHING IN THE LAB. IF I 1712 01:08:49,720 --> 01:08:51,000 A MAKE THE ACHUM SHUN LIFE 1713 01:08:51,000 --> 01:08:53,200 STARTED ON EARTH WE USE LIFE 1714 01:08:53,200 --> 01:08:54,640 EFFORTS ON EFFORT TO POINT US TO 1715 01:08:54,640 --> 01:08:55,680 THE KIND OF ENVIRONMENT WHERE IT 1716 01:08:55,680 --> 01:08:57,080 MAY HAVE STARTED, THEN I HAVE A 1717 01:08:57,080 --> 01:08:58,080 REASON TO GET UP IN THE MORNING 1718 01:08:58,080 --> 01:09:01,160 AND STUDY IT AND IT IS GREAT 1719 01:09:01,160 --> 01:09:04,320 FUN. AND I'M QUITE AWARE I MAYBE 1720 01:09:04,320 --> 01:09:05,960 DILUTING MYSELF BUT IT IS FUN 1721 01:09:05,960 --> 01:09:07,960 AND MAYBE EVERYONE RELEVANT. 1722 01:09:07,960 --> 01:09:12,320 >> SO THAT LEADS THE SECOND -- 1723 01:09:12,320 --> 01:09:14,280 THE SECOND QUESTION IS THAT 1724 01:09:14,280 --> 01:09:17,080 RELATES TO EXPERIMENT THAT YOU 1725 01:09:17,080 --> 01:09:20,560 CAN DO. SO THE INITIAL CARBON 1726 01:09:20,560 --> 01:09:22,400 FIXATION THAT YOU ARE TALKING 1727 01:09:22,400 --> 01:09:26,840 ABOUT, THESE ARE DONE WITH 1728 01:09:26,840 --> 01:09:28,840 PRESUMABLY THE INITIAL COMPOUNDS 1729 01:09:28,840 --> 01:09:31,040 ALL MIXTURES AND YET YOUR LATER 1730 01:09:31,040 --> 01:09:32,320 EXPERIMENTS AND QUITE SURE YOU 1731 01:09:32,320 --> 01:09:37,240 HAVE BEEN PUTTING THE 1732 01:09:37,240 --> 01:09:40,880 APPROPRIATE STEREO ISOMERS NOT 1733 01:09:40,880 --> 01:09:42,120 GLYCEMIC MIXTURES HOW DO YOU 1734 01:09:42,120 --> 01:09:45,920 SEE, WHAT PROCESS DO YOU SEE 1735 01:09:45,920 --> 01:09:48,120 EVOLVING THE TENDENCY TOWARD THE 1736 01:09:48,120 --> 01:09:49,080 AMINO ACID? 1737 01:09:49,080 --> 01:09:51,760 >> THE PROTERM METABOLISM, I 1738 01:09:51,760 --> 01:09:53,320 TALKED ABOUT IS NOT OBVIOUS TO 1739 01:09:53,320 --> 01:09:54,400 ME THERE WOULD BE ANY STRONG 1740 01:09:54,400 --> 01:09:57,200 PROCESSES FOR GENERATING 1741 01:09:57,200 --> 01:09:58,800 ANYTHING OTHER THAN MIXTURES. 1742 01:09:58,800 --> 01:10:01,600 SOON AS WE HAVE PEPTIDES AS A 1743 01:10:01,600 --> 01:10:05,120 MIMICKING ACTIVE SITE RIBOSYMES 1744 01:10:05,120 --> 01:10:06,760 AT KEY EARLY POINTS IN 1745 01:10:06,760 --> 01:10:07,920 METABOLISM, SO WE HAVE SOMETHING 1746 01:10:07,920 --> 01:10:09,240 APPROXIMATING A PROTEIN EARLY 1747 01:10:09,240 --> 01:10:11,400 STAGE METABOLISM, THAT HAS A 1748 01:10:11,400 --> 01:10:13,040 NECESSARY HAND IN GLOVE 1749 01:10:13,040 --> 01:10:15,000 MECHANISM AND YOU HAVE NO LONGER 1750 01:10:15,000 --> 01:10:17,200 CAN HAVE GLYCEMIC MIXTURES YOU 1751 01:10:17,200 --> 01:10:18,560 ARE OBLIGED TO FORCE METABOLISM 1752 01:10:18,560 --> 01:10:18,720 -- 1753 01:10:18,720 --> 01:10:23,400 >> GO COULD YOU MAKE THE ENZYMES 1754 01:10:23,400 --> 01:10:23,520 -- 1755 01:10:23,520 --> 01:10:25,560 >> IT COULD HAVE GONE OATHER 1756 01:10:25,560 --> 01:10:28,840 WAY. FOR SOME LIPIDS SO VISCERAL 1757 01:10:28,840 --> 01:10:32,760 PHOSPHATE IS WHAT IS SOMETIMES 1758 01:10:32,760 --> 01:10:35,600 CALLED DUAL HOMOCOMMONALITY, ALL 1759 01:10:35,600 --> 01:10:37,960 HAVE GLYCEROL 1 PHOSPHATES, ALL 1760 01:10:37,960 --> 01:10:39,640 BACTERIA HAVE GLYCEROL 3 1761 01:10:39,640 --> 01:10:43,000 PHOSPHATE, THE SAME AS THE D 1762 01:10:43,000 --> 01:10:46,960 AMINO -- L AMINO ACIDS AND L 1763 01:10:46,960 --> 01:10:48,560 SUGARS. I GET THAT THE RIGHT WAY 1764 01:10:48,560 --> 01:10:49,360 AROUND. IT WOULD HAVE BEEN THE 1765 01:10:49,360 --> 01:10:52,560 OTHER WAY. I PERMLY THINK THAT 1766 01:10:52,560 --> 01:10:54,800 THAT KIND OF (INAUDIBLE) AROSE 1767 01:10:54,800 --> 01:10:56,640 WITH GENES AND PROTEINS AND 1768 01:10:56,640 --> 01:10:59,080 GENETICALLY ENCODED METABOLISM, 1769 01:10:59,080 --> 01:11:01,600 THAT IS MY OPINION, BY NO MEANS 1770 01:11:01,600 --> 01:11:01,960 DEMONSTRATESSED. 1771 01:11:01,960 --> 01:11:04,400 >> OKAY. -- DEMONSTRATED. 1772 01:11:04,400 --> 01:11:07,000 >> REMEMBER WE CAN HOPEFULLY 1773 01:11:07,000 --> 01:11:08,680 EVERYBODY CONTINUE THE 1774 01:11:08,680 --> 01:11:11,880 DISCUSSION. WE HAVE SEVERAL 1775 01:11:11,880 --> 01:11:13,720 OTHER QUESTIONS AND FIND ONE 1776 01:11:13,720 --> 01:11:15,360 THAT INTRIGUES ME BUT I DON'T 1777 01:11:15,360 --> 01:11:16,480 THINK YOU CAN ANSWER THIS IN 1778 01:11:16,480 --> 01:11:19,520 THREE MINUTES. BUT MAYBE YOU 1779 01:11:19,520 --> 01:11:25,880 CAN. SO DOES ENERGETICS PLAY A 1780 01:11:25,880 --> 01:11:31,200 ROLE IN IT WILL CARALITY, NAMELY 1781 01:11:31,200 --> 01:11:36,200 DNA, RNA, NUCLEOTIDES, THEY ARE 1782 01:11:36,200 --> 01:11:39,400 ALL D. AND AMINO ACIDS AND 1783 01:11:39,400 --> 01:11:40,640 PROTEINS ARE -- 1784 01:11:40,640 --> 01:11:41,120 >> SOON AS YOU -- 1785 01:11:41,120 --> 01:11:44,840 >> IS THERE A ROLE FOR 1786 01:11:44,840 --> 01:11:46,880 BIOENERGETICS IN THAT PHENOMENA 1787 01:11:46,880 --> 01:11:49,240 >> I WOULD SAY NOT A DIRECT 1788 01:11:49,240 --> 01:11:52,480 ROLE. I WOULD SAY THAT AS SOON 1789 01:11:52,480 --> 01:11:57,480 AS YOU YOU ARE BEGINNING TO HAVE 1790 01:11:57,480 --> 01:12:01,080 ENZYMES THAT HAVE A POCKET THAT 1791 01:12:01,080 --> 01:12:03,480 A SUBSTRATE BINDS TO THAT POCKET 1792 01:12:03,480 --> 01:12:04,880 ONLY ONE FORM BIND TO THAT 1793 01:12:04,880 --> 01:12:07,560 POCKET SO THE FORM THAT BINDS IS 1794 01:12:07,560 --> 01:12:08,920 GOING TO DEPEND ON WHATEVER THE 1795 01:12:08,920 --> 01:12:10,680 MOST LIKELY CONFIRMATION OF 1796 01:12:10,680 --> 01:12:13,200 SMALL PEPTIDE THAT CAME OUT AND 1797 01:12:13,200 --> 01:12:15,480 I US SUSPECT YOU COME WITH 1798 01:12:15,480 --> 01:12:17,480 RATHER BLACK AN WHITE IT'S ALL L 1799 01:12:17,480 --> 01:12:20,160 OR ALL D, YOU PROBABLY HAVE SOME 1800 01:12:20,160 --> 01:12:23,200 BIAS OR SHIFT TOWARDS ONE OR THE 1801 01:12:23,200 --> 01:12:25,400 OTHER BUT YOU ONLY NEED HANDFUL 1802 01:12:25,400 --> 01:12:29,920 OF PLACES IN METABOLISM TO HAVE 1803 01:12:29,920 --> 01:12:31,720 PEPTIDES THAT WILL BIND ONLY ONE 1804 01:12:31,720 --> 01:12:36,120 OF THE ISOMERS TO GIVE YOU 1805 01:12:36,120 --> 01:12:37,360 CARALITY AS WE KNOW IT. I DON'T 1806 01:12:37,360 --> 01:12:40,160 THINK THERE'S A NEED TO SAY YOU 1807 01:12:40,160 --> 01:12:42,360 CAN HAVE SLIGHT BIAS IN L VERSUS 1808 01:12:42,360 --> 01:12:44,800 D FORMS ON MYYOURATE IN SPACE 1809 01:12:44,800 --> 01:12:47,000 AND BECAME AMPLIFIED, THAT COULD 1810 01:12:47,000 --> 01:12:48,240 BE OVERWRITTEN SOON AS YOU HAVE 1811 01:12:48,240 --> 01:12:50,240 ENZYMES THEY ARE GOING TO IMPOSE 1812 01:12:50,240 --> 01:12:51,720 A -- ON YOU WHETHER YOU LIKE T 1813 01:12:51,720 --> 01:12:54,920 OR NOT. PROBABLY AMPLIFY 1814 01:12:54,920 --> 01:12:56,240 PRE-EXISTING BIAS BUT THAT IS 1815 01:12:56,240 --> 01:12:58,360 NOT DIRECTLY ENERGETIC BUT FLUX 1816 01:12:58,360 --> 01:13:00,520 HAS TO GO THROUGH THE SYSTEM SO 1817 01:13:00,520 --> 01:13:02,280 IT IS INDIRECTLY. 1818 01:13:02,280 --> 01:13:07,520 >> OKAY. CHRIS, FROM THE -- NICK 1819 01:13:07,520 --> 01:13:08,920 FROM THE QUESTIONS AND 1820 01:13:08,920 --> 01:13:09,840 ALL WE HAVE RECEIVED THE 1821 01:13:09,840 --> 01:13:12,040 UNDERLYING MESSAGE IS WE HAVE TO 1822 01:13:12,040 --> 01:13:15,360 HAVE YOU COME VISIT HERE AGAIN. 1823 01:13:15,360 --> 01:13:16,320 >> THAT WOULD BE GREAT. 1824 01:13:16,320 --> 01:13:19,080 >> OPENED UP AN ENORMOUS AREAS 1825 01:13:19,080 --> 01:13:22,000 THAT NORMALLY I THINK MOST OF US 1826 01:13:22,000 --> 01:13:23,080 DON'T REGULARLY THINK ABOUT. BUT 1827 01:13:23,080 --> 01:13:26,840 SHOULD. ON BEHALF OF EVERYBODY 1828 01:13:26,840 --> 01:13:30,400 HERE, OUT THERE, THE NIH, WE ARE 1829 01:13:30,400 --> 01:13:31,920 MOST DELIGHTED YOU ARE HERE, 1830 01:13:31,920 --> 01:13:34,760 THANK YOU VERY MUCH FOR A VERY 1831 01:13:34,760 --> 01:13:35,480 EXCITING PRESENTATION AND 1832 01:13:35,480 --> 01:13:38,040 EVERYONE IS NOW WELCOME TO A 1833 01:13:38,040 --> 01:13:40,760 BOOK SIGNING WHICH IS OUTSIDE IN 1834 01:13:40,760 --> 01:13:47,160 THE RECEPTION AREA. THANK YOU. 1835 01:13:47,160 --> 01:13:57,360 [APPLAUSE]