1 00:00:01,000 --> 00:00:04,000 [music playing] 2 00:00:16,266 --> 00:00:18,100 - I'M REALLY HAPPY AGAIN HERE 3 00:00:18,100 --> 00:00:22,400 TO WELCOME ALL OF YOU TO THIS INSTALLMENT 4 00:00:22,400 --> 00:00:24,866 OF THE 75TH ANNIVERSARY CELEBRATION 5 00:00:24,866 --> 00:00:26,266 OF NASA AMES RESEARCH CENTER 6 00:00:26,266 --> 00:00:29,466 AND THE DIRECTOR'S COLLOQUIUM SUMMER SERIES. 7 00:00:31,266 --> 00:00:33,700 THE--NOW, THIS IS PARTICULARLY, AS A LOT OF YOU KNOW, 8 00:00:33,700 --> 00:00:35,666 IS FOCUSED ON, YOU KNOW, 9 00:00:35,666 --> 00:00:37,433 OUR STUDENTS THAT ARE HERE DURING THE SUMMER, 10 00:00:37,433 --> 00:00:38,866 BUT IT'S ALSO FOCUSED ON THE REST OF US 11 00:00:38,866 --> 00:00:40,766 WHO, YOU KNOW, LIKE ME, I'M A BUREAUCRAT. 12 00:00:40,766 --> 00:00:43,400 I DON'T REALLY GET A CHANCE TO HEAR COOL STUFF. 13 00:00:43,400 --> 00:00:46,100 SO I'M LOOKING FORWARD TO THIS. 14 00:00:46,100 --> 00:00:48,133 TODAY, WE HAVE DR. JOSH ALWOOD. 15 00:00:48,133 --> 00:00:50,800 HE'S A RESEARCH SCIENTIST IN THE SPACE BIOSCIENCES DIVISION 16 00:00:50,800 --> 00:00:52,700 HERE AT NASA AMES RESEARCH CENTER. 17 00:00:52,700 --> 00:00:54,566 AND AS I'LL TELL YOU IN A MOMENT, 18 00:00:54,566 --> 00:00:56,300 YOU KNOW, I'M KIND OF ENVIOUS, 19 00:00:56,300 --> 00:00:58,466 BECAUSE HE HAS A BACKGROUND KIND OF SIMILAR TO MINE. 20 00:00:58,466 --> 00:01:00,133 HE STUDIED PHYSICS AND ASTRONOMY 21 00:01:00,133 --> 00:01:02,266 AND, YOU KNOW, THEN WENT AND DID SOME ENGINEERING STUFF 22 00:01:02,266 --> 00:01:05,333 AND--AND HE SORT OF TRANSITIONED TO, YOU KNOW, BIOLOGY, 23 00:01:05,333 --> 00:01:07,033 WHICH I THINK IS REALLY IMPORTANT. 24 00:01:07,033 --> 00:01:08,633 WHEREAS I'M TOO OLD TO UNDERSTAND 25 00:01:08,633 --> 00:01:10,033 ALL THE BIOLOGY STUFF. 26 00:01:10,033 --> 00:01:11,766 SOMEBODY TRIED TO TELL ME ABOUT CELLS, 27 00:01:11,766 --> 00:01:15,333 AND SAID, YOU KNOW--YOU KNOW, THE ONLY CELLS I KNOW 28 00:01:15,333 --> 00:01:17,633 IS WHEN I WENT AND VISITED SAN QUENTIN. 29 00:01:17,633 --> 00:01:19,166 [laughter] 30 00:01:19,166 --> 00:01:21,666 BUT, YOU KNOW, JUST TO KIND OF REVIEW A LITTLE BIT, 31 00:01:21,666 --> 00:01:23,800 THE MISSION OF THE BIOSCIENCES RESEARCH BRANCH 32 00:01:23,800 --> 00:01:26,533 IS TO ADVANCE SPACE EXPLORATION 33 00:01:26,533 --> 00:01:29,500 BY NEW SCIENTIFIC DISCOVERIES 34 00:01:29,500 --> 00:01:32,533 IN--IN TECHNOLOGICAL DEVELOPMENTS IN BIOLOGY. 35 00:01:32,533 --> 00:01:35,000 AND THIS--THIS PARTICULAR RESEARCH 36 00:01:35,000 --> 00:01:37,166 IS GOING TO REVEAL REALLY IMPORTANT CLUES 37 00:01:37,166 --> 00:01:40,766 ABOUT WHAT CAUSES OSTEOPOROSIS AND OTHER BONE DISORDERS. 38 00:01:40,766 --> 00:01:42,766 WHEN YOU GET MY AGE, IT'S REALLY INTERESTING 39 00:01:42,766 --> 00:01:44,700 TO HEAR ABOUT THOSE. 40 00:01:44,700 --> 00:01:47,466 AND HIS PRIMARY FOCUS IS UNDER-- EXAMINING HOW SPACEFLIGHT 41 00:01:47,466 --> 00:01:50,800 AND MECHANICAL LOADING TRIGGERS COMPLEX CHANGES IN ORGANISMS, 42 00:01:50,800 --> 00:01:52,966 PARTICULARLY THE MAMMALIAN SKELETON. 43 00:01:52,966 --> 00:01:55,533 HE RECEIVED HIS PhD FROM STANFORD UNIVERSITY-- 44 00:01:55,533 --> 00:01:57,133 IT'S A JUNIOR COLLEGE UP THE ROAD HERE, 45 00:01:57,133 --> 00:01:58,166 FOR THOSE THAT DON'T KNOW-- [laughter] 46 00:01:58,166 --> 00:01:59,766 IN AERONAUTICS AND ASTRONAUTICS. 47 00:01:59,766 --> 00:02:01,233 AND HIS BACHELOR OF SCIENCE DEGREE 48 00:02:01,233 --> 00:02:03,500 FROM THE UNIVERSITY OF FLORIDA IN PHYSICS AND ASTRONOMY. 49 00:02:03,500 --> 00:02:07,433 YOU KNOW, ANOTHER, YOU KNOW, SEMI-WELL-KNOWN PLACE. 50 00:02:07,433 --> 00:02:09,766 HE COULDN'T GET INTO MICHIGAN. 51 00:02:09,766 --> 00:02:11,200 [laughter] 52 00:02:11,200 --> 00:02:12,966 BUT I--ALL-- ALL KIDDING ASIDE. 53 00:02:12,966 --> 00:02:16,233 JOSH IS ONE OF OUR MOST DISTINGUISHED RESEARCHERS. 54 00:02:16,233 --> 00:02:20,466 HE RECENTLY COMPLETED HIS NASA POSTDOCTORAL PROGRAM 55 00:02:20,466 --> 00:02:22,100 HERE AT AMES. 56 00:02:22,100 --> 00:02:25,533 BUT ON APRIL OF THIS YEAR, AND I AM REALLY PROUD OF JOSH 57 00:02:25,533 --> 00:02:27,233 AND I THINK THAT THE WHOLE CENTER SHOULD BE, 58 00:02:27,233 --> 00:02:28,866 HE WAS HONORED AT THE WHITE HOUSE-- 59 00:02:28,866 --> 00:02:30,933 SOME OF YOU MIGHT HAVE HEARD OF THAT-- 60 00:02:30,933 --> 00:02:33,133 BY PRESIDENT OBAMA--SOME OF YOU MIGHT HAVE HEARD OF HIM-- 61 00:02:33,133 --> 00:02:35,166 AND HE WAS NAMED ONE-- 62 00:02:35,166 --> 00:02:38,266 HE WAS ONE OF THE FIVE NASA RESEARCHERS 63 00:02:38,266 --> 00:02:40,500 THAT WAS A RECIPIENT OF THE 2012 64 00:02:40,500 --> 00:02:43,100 PRESIDENTIAL EARLY CAREER AWARD FOR SCIENTISTS AND ENGINEERS. 65 00:02:43,100 --> 00:02:45,600 SO JOSH IS GONNA TALK TODAY 66 00:02:45,600 --> 00:02:48,966 ABOUT "TO THE BONE: SPACEFLIGHT AND THE SKELETAL SYSTEM." 67 00:02:48,966 --> 00:02:51,566 I ALSO NOTE, YOU KNOW-- 68 00:02:51,566 --> 00:02:54,833 YOU KNOW, SINCE I WORE KIND OF AN INTERESTING OUTFIT, 69 00:02:54,833 --> 00:02:56,566 THAT JOSH HAS TODAY, TOO, 70 00:02:56,566 --> 00:02:57,933 'CAUSE YOU USUALLY DON'T SEE HIM IN A SUIT. 71 00:02:57,933 --> 00:03:01,266 SO PLEASE JOIN ME IN WELCOMING DR. JOSH ALWOOD. 72 00:03:01,266 --> 00:03:04,366 [applause] 73 00:03:04,366 --> 00:03:08,166 - THANK YOU, PETE. 74 00:03:08,166 --> 00:03:10,300 WELL, THANK YOU FOR THE INTRODUCTION, PETE. 75 00:03:10,300 --> 00:03:13,133 AND THANK YOU FOR INVITING ME TO PARTICIPATE 76 00:03:13,133 --> 00:03:15,500 IN THIS COLLOQUIUM SERIES THIS SUMMER. 77 00:03:15,500 --> 00:03:17,900 AND AS YOU CAN TELL BY THE PROPS ON THE STAGE 78 00:03:17,900 --> 00:03:20,400 AND THE MUSIC, THE--THE PERSIAN RUG, 79 00:03:20,400 --> 00:03:22,400 WE'RE GONNA HAVE A LITTLE BIT OF FUN TODAY. 80 00:03:22,400 --> 00:03:24,466 AND I WAS CHALLENGED TO WEAR A COSTUME, 81 00:03:24,466 --> 00:03:26,466 AND I DIDN'T--I WOULDN'T HAVE COUNTED THIS AS A COSTUME, 82 00:03:26,466 --> 00:03:30,433 BUT I GUARANTEE ONE COSTUME DURING THE PRESENTATION TODAY. 83 00:03:30,433 --> 00:03:33,066 SO KEEP YOUR EYES OPEN. 84 00:03:33,066 --> 00:03:35,933 SO, AS PETE SAID, I'M A NEWLY HIRED SCIENTIST HERE 85 00:03:35,933 --> 00:03:38,266 AT NASA AMES IN SPACE BIOLOGY. 86 00:03:38,266 --> 00:03:40,533 IN TODAY'S TALK, I'D LIKE TO BROADLY COVER 87 00:03:40,533 --> 00:03:44,033 THE BODY OF KNOWLEDGE IN SKELETAL BIOLOGY 88 00:03:44,033 --> 00:03:46,500 AND BIOMECHANICS DURING SPACEFLIGHT. 89 00:03:46,500 --> 00:03:49,400 AND I AM TO CONVEY THE RISKS OF BONE LOSS 90 00:03:49,400 --> 00:03:50,966 DURING THE SPACE MISSIONS 91 00:03:50,966 --> 00:03:53,133 AND THAT RESEARCH-- FUNDAMENTAL RESEARCH 92 00:03:53,133 --> 00:03:55,800 IN THIS AREA IS AN IMPORTANT COMPONENT OF ANY SPACE PROGRAM 93 00:03:55,800 --> 00:03:57,366 FOR TWO REASONS-- 94 00:03:57,366 --> 00:04:01,066 THE FIRST BEING TO UNCOVER BASIC BIOLOGICAL MECHANISMS 95 00:04:01,066 --> 00:04:03,633 THAT IMPROVE OUR UNDERSTANDING OF THESE CONDITIONS, 96 00:04:03,633 --> 00:04:07,200 AS WELL AS TO TEST PROTECTIVE TREATMENTS, 97 00:04:07,200 --> 00:04:10,133 REFERRED TO IN THE TALK AS COUNTERMEASURES, 98 00:04:10,133 --> 00:04:12,433 THAT ENABLE HUMAN EXPLORATION OF SPACE. 99 00:04:12,433 --> 00:04:14,200 AND THIS IS A PROCESS 100 00:04:14,200 --> 00:04:16,200 OF TRANSLATING BASIC SCIENCE RESULTS 101 00:04:16,200 --> 00:04:18,900 INTO--INTO PRACTICE AND INTO SOLUTIONS. 102 00:04:18,900 --> 00:04:22,600 AND THIS IS NICELY ENCAPSULATED BY THE AMES LOGO, ACTUALLY-- 103 00:04:22,600 --> 00:04:25,366 DISCOVERY LEADING TO INNOVATIONS LEADING TO SOLUTIONS. 104 00:04:25,366 --> 00:04:27,866 AND YOU CAN SEE THE LITTLE CELL-- 105 00:04:27,866 --> 00:04:30,300 THE FLUORESCENT GREEN HERE ARE CELLS, 106 00:04:30,300 --> 00:04:33,800 AND SO THAT REALLY ILLUSTRATES THE PROCESS WE'LL BE TAKING 107 00:04:33,800 --> 00:04:35,766 WITH THIS TRANSLATIONAL PIPELINE. 108 00:04:35,766 --> 00:04:37,133 AND WHEN I WAS AT THE WHITE HOUSE, 109 00:04:37,133 --> 00:04:39,733 PRESIDENT OBAMA ACTUALLY IS VERY IN TUNE 110 00:04:39,733 --> 00:04:41,500 WITH TRANSLATIONAL RESEARCH. 111 00:04:41,500 --> 00:04:44,066 HE ACTUALLY EMPHASIZED THAT IT'S REALLY IMPORTANT 112 00:04:44,066 --> 00:04:46,066 FOR BASIC SCIENTISTS TO TRANSLATE THEIR WORK 113 00:04:46,066 --> 00:04:49,100 TO HELP HUMAN PROBLEMS. 114 00:04:49,100 --> 00:04:52,600 SO IF I HAD TO SUMMARIZE MY TALK IN ONE SLIDE, 115 00:04:52,600 --> 00:04:54,466 SPACEFLIGHT IS BAD FOR THE BONE 116 00:04:54,466 --> 00:04:56,400 THOROGOOD ALMOST GOT IT RIGHT. 117 00:04:56,400 --> 00:05:00,966 AND SO SPACEFLIGHT IS--PRESENTS UNIQUE BIOLOGICAL CHALLENGES 118 00:05:00,966 --> 00:05:04,600 TO THE SURVIVAL AND EQUILIBRIUM OF LIVING SYSTEMS. 119 00:05:04,600 --> 00:05:07,566 AND TWO NOTABLE ASPECTS OF THE ENVIRONMENT 120 00:05:07,566 --> 00:05:10,266 ARE WEIGHTLESSNESS ASSOCIATED WITH MICROGRAVITY 121 00:05:10,266 --> 00:05:12,800 AS WELL AS IONIZING RADIATION EXPOSURE 122 00:05:12,800 --> 00:05:15,966 FROM SOLAR PARTICLE EVENTS, WHICH ARE MAINLY PROTONS 123 00:05:15,966 --> 00:05:19,766 AND GALACTIC COSMIC RAYS, WHICH ARE VERY HIGH ENERGY 124 00:05:19,766 --> 00:05:22,800 AND VERY HARD TO SHIELD AND CAN-- 125 00:05:22,800 --> 00:05:26,300 AND DO GREAT DAMAGE IN BIOLOGICAL ORGANISMS. 126 00:05:26,300 --> 00:05:29,566 IT'S WIDELY KNOWN THAT WEIGHTLESSNESS 127 00:05:29,566 --> 00:05:31,333 INDUCES BONE LOSS, 128 00:05:31,333 --> 00:05:34,300 BUT LESS WELL-KNOWN ARE THE EFFECTS OF SPACE RADIATION. 129 00:05:34,300 --> 00:05:36,166 AND THIS WILL BECOME VERY IMPORTANT 130 00:05:36,166 --> 00:05:38,266 ONCE WE VENTURE OUTSIDE OF THE EARTH'S MAGNETIC FIELDS, 131 00:05:38,266 --> 00:05:39,666 WHICH ARE CURRENTLY PROTECTING US 132 00:05:39,666 --> 00:05:42,400 FROM SOME OF THESE HIGH-ENERGY COSMIC RAYS. 133 00:05:42,400 --> 00:05:45,200 AND SO THIS KIND OF ILLUSTRATES THAT TRANSLATIONAL PIPELINE. 134 00:05:45,200 --> 00:05:47,433 WHY DO WE STUDY BONE LOSS? 135 00:05:47,433 --> 00:05:50,366 WELL, THERE'S THE BASIC HYPOTHESIS-DRIVEN SCIENCE 136 00:05:50,366 --> 00:05:53,800 AND DISCOVERY OF NEW KNOWLEDGE 137 00:05:53,800 --> 00:05:56,866 BUT ALSO TRYING TO ENABLE LONGER DURATION MISSIONS 138 00:05:56,866 --> 00:05:59,200 THAT ARE FARTHER AWAY FROM OUR HOME HERE ON EARTH. 139 00:05:59,200 --> 00:06:02,566 AT THE SAME TIME, WE ALSO WANT TO HELP PEOPLE ON EARTH 140 00:06:02,566 --> 00:06:05,900 IN TERMS OF UNDERSTANDING OSTEOPOROSIS BETTER, 141 00:06:05,900 --> 00:06:08,633 UNDERSTANDING WHAT IS-- 142 00:06:08,633 --> 00:06:10,700 WHAT ARE THE MECHANISMS OF AGING, 143 00:06:10,700 --> 00:06:14,166 WHAT ARE THE NEGATIVE EFFECTS OF BED REST, SEDENTARY LIFESTYLES, 144 00:06:14,166 --> 00:06:17,033 RADIATION ON-- FROM OCCUPATIONAL EXPOSURE 145 00:06:17,033 --> 00:06:19,800 AND RADIO THERAPY, AND THINKING BIG, 146 00:06:19,800 --> 00:06:23,033 OPENING UP NEW POSSIBILITIES FOR HUMANITY'S ROLE IN SPACE. 147 00:06:23,033 --> 00:06:25,233 BEFORE I DELVE INTO SCIENCE, 148 00:06:25,233 --> 00:06:27,766 I'D LIKE TO SHARE WHERE MY INTEREST ORIGINATED FROM 149 00:06:27,766 --> 00:06:30,000 AND THE PATH I TOOK TO BECOME A SCIENTIST. 150 00:06:30,000 --> 00:06:32,233 AND AS YOU HEARD IN THE INTRODUCTION, 151 00:06:32,233 --> 00:06:34,166 MY BACKGROUND IS SOMEWHAT STAGGERED. 152 00:06:34,166 --> 00:06:36,866 BUT LOOKING BACK, I WAS PURSUING AN INTEREST 153 00:06:36,866 --> 00:06:41,066 THAT RESIDED IN THE NEXUS OF THREE SEEMINGLY SEPARATE AREAS, 154 00:06:41,066 --> 00:06:43,433 AND I'VE KIND OF GENERALIZED THESE ELEMENTS 155 00:06:43,433 --> 00:06:46,033 AS FORCE, LIFE, AND SPACE. 156 00:06:46,033 --> 00:06:49,533 AND SO I THINK IT STARTED WITH SCIENTIFIC CURIOSITY, 157 00:06:49,533 --> 00:06:52,233 ASKING QUESTIONS, SEEKING UNDERSTANDING, 158 00:06:52,233 --> 00:06:54,533 AND THEN WITH-- WITH MY RESEARCH, 159 00:06:54,533 --> 00:06:56,533 LEARNING HOW TO FORM A HYPOTHESIS 160 00:06:56,533 --> 00:06:59,233 AND--AND ANSWER THAT HYPOTHESIS. 161 00:06:59,233 --> 00:07:00,833 I GREW UP IN FLORIDA 162 00:07:00,833 --> 00:07:03,933 AND WAS REALLY ABLE TO SEE FIRSTHAND 163 00:07:03,933 --> 00:07:05,633 THE SPACE SHUTTLE LAUNCHES. 164 00:07:05,633 --> 00:07:08,200 AND SO THIS IS A PICTURE I TOOK IN HIGH SCHOOL, 165 00:07:08,200 --> 00:07:11,166 AND THIS REALLY CAPTIVATED MY IMAGINATION 166 00:07:11,166 --> 00:07:13,866 AND PROPELLED ME INTO STUDYING PHYSICS 167 00:07:13,866 --> 00:07:17,366 AND, LATER, STRUCTURAL ENGINEERING. 168 00:07:17,366 --> 00:07:20,166 AND SO IF ANY OF YOU RECOGNIZE 169 00:07:20,166 --> 00:07:21,433 THE LAST FORMULA THERE, 170 00:07:21,433 --> 00:07:23,166 YOU CAN GO AHEAD AND HEAD TO THE RECEPTION, 171 00:07:23,166 --> 00:07:25,466 'CAUSE YOU'LL--YOU UNDERSTAND THE TALK ALREADY. 172 00:07:25,466 --> 00:07:28,500 AND SO I THINK I WAS-- 173 00:07:28,500 --> 00:07:32,266 FROM MY CHILDHOOD, WHEN I WAS ABOUT MAYBE HALF THE SIZE 174 00:07:32,266 --> 00:07:34,266 THAT I CURRENTLY AM, 175 00:07:34,266 --> 00:07:37,500 I WAS FASCINATED WITH BONE AS A LIVING STRUCTURE-- 176 00:07:37,500 --> 00:07:40,600 AND I'LL KIND OF EXPLAIN WHAT A LIVING STRUCTURE IS 177 00:07:40,600 --> 00:07:43,833 IN A COUPLE SLIDES-- 178 00:07:43,833 --> 00:07:48,033 BUT I REALLY IMMERSED INTO SKELETAL BIOLOGY RESEARCH 179 00:07:48,033 --> 00:07:51,233 AND--AND SO THE THING THAT TIES THIS ALL TOGETHER 180 00:07:51,233 --> 00:07:55,000 IS THE EFFECTS OF SPACEFLIGHT ON THE HUMAN BODY 181 00:07:55,000 --> 00:07:57,700 AND ON THE SKELETON. 182 00:07:59,233 --> 00:08:01,633 I'VE ALSO--I ALSO SOON IMMERSED IN-- 183 00:08:01,633 --> 00:08:03,300 FOLLOWING HIGH SCHOOL, 184 00:08:03,300 --> 00:08:05,133 IMMERSED IN SCIENTIFIC RESEARCH. 185 00:08:05,133 --> 00:08:08,433 AND WAS A PARTICIPANT IN A NUMBER OF PROGRAMS, 186 00:08:08,433 --> 00:08:10,000 EDUCATIONAL PROGRAMS. 187 00:08:10,000 --> 00:08:12,333 AND I WANT TO EMPHASIZE TO THE STUDENTS IN THE AUDIENCE, 188 00:08:12,333 --> 00:08:14,633 YOU ALREADY KNOW THIS, BUT GET INVOLVED, 189 00:08:14,633 --> 00:08:18,100 BROADEN YOUR INTERESTS, AND--AND REALLY DEVELOP 190 00:08:18,100 --> 00:08:20,400 YOUR--YOUR EXPERTISE AND INTERESTS. 191 00:08:20,400 --> 00:08:23,533 AND THOSE ON THE WEB, HERE ARE SOME PROGRAMS 192 00:08:23,533 --> 00:08:26,233 THAT NASA PROVIDES. 193 00:08:26,233 --> 00:08:28,366 SO MOVING NOW TO THE SCIENCE. 194 00:08:28,366 --> 00:08:30,200 I'LL START AT THE STRUCTURAL LEVEL. 195 00:08:30,200 --> 00:08:34,500 SO THINKING ABOUT BONES AS LIVING STRUCTURES, 196 00:08:34,500 --> 00:08:36,533 AND SO WHAT I HAVE HERE 197 00:08:36,533 --> 00:08:39,033 IS A RAT SKELETON AND A HUMAN SKELETON, 198 00:08:39,033 --> 00:08:41,700 JUST TO COMPARE AND CONTRAST THE DIFFERENT 199 00:08:41,700 --> 00:08:44,466 MORPHOLOGIES AND SIZES 200 00:08:44,466 --> 00:08:47,233 AND THAT RESEARCH WITH SOME OF THESE MODEL ORGANISMS 201 00:08:47,233 --> 00:08:49,000 CAN COMPLEMENT OUR KNOWLEDGE 202 00:08:49,000 --> 00:08:51,633 OF BONE LOSS IN ASTRONAUTS. 203 00:08:51,633 --> 00:08:53,333 AND THEN I'LL PROGRESSIVELY GO 204 00:08:53,333 --> 00:08:55,100 TO SMALLER AND SMALLER LINK SCALES 205 00:08:55,100 --> 00:08:57,033 SO THEN WORKING AT THE CELLULAR LEVEL 206 00:08:57,033 --> 00:09:00,533 AS WELL AS THE MOLECULAR LEVEL. 207 00:09:00,533 --> 00:09:03,233 SO IN ADDITION TO SKELETAL EFFECTS, 208 00:09:03,233 --> 00:09:07,600 GENERALLY SPACEFLIGHT IS BAD FOR THE ENTIRE BODY. 209 00:09:07,600 --> 00:09:11,800 AMONG A NUMBER OF RESPONSES IN THE BODY, 210 00:09:11,800 --> 00:09:14,266 THERE'S FLUID REDISTRIBUTION TO THE TORSO, 211 00:09:14,266 --> 00:09:17,166 THERE ARE VISUAL CHANGES, AMONG OTHERS. 212 00:09:17,166 --> 00:09:19,533 AND WE--YOU KNOW, THIS UNDERSCORES 213 00:09:19,533 --> 00:09:21,166 THAT WE'VE EVOLVED AT 1G. 214 00:09:21,166 --> 00:09:22,966 IT'S BEEN CONSTANT. 215 00:09:22,966 --> 00:09:25,200 AND WE INTIMATELY DEPEND ON GRAVITY 216 00:09:25,200 --> 00:09:27,200 FOR--FOR SKELETAL HOMEOSTASIS 217 00:09:27,200 --> 00:09:29,566 AND HOMEOSTASIS IN THE BODY. 218 00:09:29,566 --> 00:09:31,566 IT'S AN INTERESTING FACT 219 00:09:31,566 --> 00:09:33,333 THAT BREAKING DOWN THE BONE MAY INCREASE-- 220 00:09:33,333 --> 00:09:36,266 LEAD TO INCREASED RISK OF KIDNEY STONES 221 00:09:36,266 --> 00:09:39,766 AS THE CALCIUM IS EXCRETED IN THE URINE. 222 00:09:39,766 --> 00:09:42,700 AND THIS--THIS HAS BECOME A PROBLEM 223 00:09:42,700 --> 00:09:45,233 IN THE PLUMBING ON ISS. 224 00:09:45,233 --> 00:09:48,800 SO THIS IS--YOU KNOW, SPACEFLIGHT IS BAD 225 00:09:48,800 --> 00:09:50,966 AND THE LOSS OF SKELETAL MINERAL IS BAD 226 00:09:50,966 --> 00:09:52,733 FOR THE ISS HARDWARE AS WELL. 227 00:09:52,733 --> 00:09:55,300 THIS IS A URINE PROCESSING ASSEMBLY 228 00:09:55,300 --> 00:09:57,366 THAT RECYCLES URINE INTO DRINKING WATER. 229 00:09:57,366 --> 00:10:01,200 AND--AND THIS WAS ACTUALLY CLOGGED 230 00:10:01,200 --> 00:10:04,066 BY ELEVATED CALCIUM CONCENTRATIONS, 231 00:10:04,066 --> 00:10:07,800 IN PART DUE TO THE HEIGHTENED BONE LOSS IN ASTRONAUTS. 232 00:10:09,533 --> 00:10:14,166 GETTING BACK TO THE SKELETON AS A LIVING STRUCTURE. 233 00:10:14,166 --> 00:10:15,666 THIS IS--THIS IS ONE REASON 234 00:10:15,666 --> 00:10:19,400 WHY BONE REALLY FASCINATES ME. 235 00:10:19,400 --> 00:10:21,500 WHAT DOES A LIVING STRUCTURE MEAN? 236 00:10:21,500 --> 00:10:25,233 WELL, CONTRAST BONE TO A BRIDGE 237 00:10:25,233 --> 00:10:27,300 MADE OF CONCRETE AND STEEL. 238 00:10:27,300 --> 00:10:30,966 THEY BOTH CARRY THE EFFECTIVE LOAD, AND-- 239 00:10:30,966 --> 00:10:33,166 HOWEVER, THE SKELETON ACTIVELY SENSES 240 00:10:33,166 --> 00:10:36,033 AND ADAPTS TO THE DEMANDS OF ITS MECHANICAL ENVIRONMENT-- 241 00:10:36,033 --> 00:10:38,833 LIKE MUSCULAR FORCES, GROUND REACTION FORCES-- 242 00:10:38,833 --> 00:10:42,266 BY DISTRIBUTING MINERAL-- MINERALIZED TISSUE 243 00:10:42,266 --> 00:10:45,733 WHERE IT'S MOST NEEDED AND REMOVING IT WHERE IT'S NOT. 244 00:10:45,733 --> 00:10:47,533 AND SO OVER--THIS IS-- 245 00:10:47,533 --> 00:10:50,000 THIS LINE OF THINKING EXTENDS BACK OVER 100 YEARS 246 00:10:50,000 --> 00:10:53,200 WITH AN ORTHOPEDIST NAMED JULIUS WOLFF 247 00:10:53,200 --> 00:10:54,566 WHERE HE PROPOSED THESE IDEAS 248 00:10:54,566 --> 00:10:57,366 AFTER OBSERVING THE ORGANIZATION OF THE FEMORAL HEAD. 249 00:10:57,366 --> 00:10:59,500 AND SO THAT'S SHOWN IN CROSS SECTION HERE. 250 00:10:59,500 --> 00:11:02,066 SO THIS IS THE HIP JOINT 251 00:11:02,066 --> 00:11:04,266 KIND OF IN-- THIS IS THE PROXIMAL-- 252 00:11:04,266 --> 00:11:06,966 PROXIMAL FEMUR IN A LONGITUDINAL CROSS SECTION. 253 00:11:06,966 --> 00:11:09,466 NOW, WHAT YOU SEE WHEN YOU CRACK OPEN A FEMUR 254 00:11:09,466 --> 00:11:12,000 IS YOU SEE KIND OF THIS HOLLOW TUBULAR STRUCTURE 255 00:11:12,000 --> 00:11:13,666 IN THE MIDSHAFT, 256 00:11:13,666 --> 00:11:16,266 WHICH IS THE REALLY, REALLY DENSE CORTICAL BONE. 257 00:11:16,266 --> 00:11:18,633 AS YOU GET UP TO THE JOINT, THE HIP JOINT, 258 00:11:18,633 --> 00:11:22,233 YOU SEE THIS VERY-- HIGHLY STRIATED 259 00:11:22,233 --> 00:11:25,700 AND HIGHLY POROUS CANCELLOUS OR TRABECULAR BONE. 260 00:11:25,700 --> 00:11:27,566 AND WHAT WOLFF RECOGNIZED 261 00:11:27,566 --> 00:11:30,600 IS THAT LIKE A CANTILEVERED BEAM AND BENDING, 262 00:11:30,600 --> 00:11:33,766 THE FEMUR HAS COMPRESSIVE STRUTS. 263 00:11:33,766 --> 00:11:35,300 IT HAS TENSILE STRUTS, 264 00:11:35,300 --> 00:11:37,266 AND THAT THESE ARE UNIQUE LOAD PATHS 265 00:11:37,266 --> 00:11:39,400 THAT TRANSFER FORCE INTO THE CORTICAL BONE. 266 00:11:41,300 --> 00:11:45,133 IT'S IMPORTANT TO NOTE THAT LOCATIONS OF FRACTURE 267 00:11:45,133 --> 00:11:47,100 IN OSTEOPOROTIC PATIENTS, 268 00:11:47,100 --> 00:11:49,433 AS WELL AS POTENTIALLY IN ASTRONAUTS, 269 00:11:49,433 --> 00:11:52,700 OCCURS IN THESE HIGHLY POROUS CANCELLOUS REGIONS. 270 00:11:52,700 --> 00:11:55,033 SO IF YOU DISTURB THE--THE TISSUE THERE, 271 00:11:55,033 --> 00:11:57,933 IT'S VERY FRAGILE TISSUE 272 00:11:57,933 --> 00:12:00,666 AND THAT CAN LEAD TO A HEIGHTENED PROPENSITY 273 00:12:00,666 --> 00:12:04,100 FOR FRACTURE. 274 00:12:04,100 --> 00:12:05,966 ZOOMING IN NOW TO THE CELLULAR LEVEL, 275 00:12:05,966 --> 00:12:08,966 THERE ARE THREE CELL TYPES THAT I'LL TALK ABOUT TODAY. 276 00:12:08,966 --> 00:12:12,333 THE FIRST IS THE OSTEOBLAST 277 00:12:12,333 --> 00:12:13,966 THESE ARE BONE-FORMING CELLS 278 00:12:13,966 --> 00:12:16,166 THAT RESIDE AT THE SURFACE OF THE BONE. 279 00:12:16,166 --> 00:12:19,500 OCCASIONALLY, SOME OF THESE OSTEOBLAST CELLS 280 00:12:19,500 --> 00:12:21,866 BECOME TRAPPED IN THEIR OWN MATRIX 281 00:12:21,866 --> 00:12:23,533 IN MINERALIZED TISSUE 282 00:12:23,533 --> 00:12:26,900 AND BECOME EMBEDDED INTO CAVE-LIKE LACUNAE, 283 00:12:26,900 --> 00:12:29,666 AND THESE ARE DEEMED OSTEOCYTES. 284 00:12:32,100 --> 00:12:35,766 THERE'S A THIRD TYPE OF CELL CALLED OSTEOCLASTS, 285 00:12:35,766 --> 00:12:38,933 AND THESE ARE GIANT MULTINUCLEATED CELLS 286 00:12:38,933 --> 00:12:40,300 THAT ATTACH TO THE BONE 287 00:12:40,300 --> 00:12:43,300 AND DISSOLVE AWAY THIS MATRIX AND MINERAL. 288 00:12:43,300 --> 00:12:46,066 AND COORDINATED--COORDINATED ACTIVITY OF THESE CELLS 289 00:12:46,066 --> 00:12:50,033 IS CALLED BONE REMODELING AND ALLOW SHAPING OF THE BONE, 290 00:12:50,033 --> 00:12:52,533 AND IT'S A REMARKABLY DYNAMIC PROCESS. 291 00:12:52,533 --> 00:12:55,666 FOR EXAMPLE, THE SKELETON COMPLETELY REMODELS ITSELF 292 00:12:55,666 --> 00:12:57,733 ABOUT ONCE EVERY DECADE. 293 00:12:57,733 --> 00:13:01,366 LOOKING AT THE ULTRASTRUCTURE OF THE OSTEOCYTE, 294 00:13:01,366 --> 00:13:03,066 WHICH IS IN THE LOWER RIGHT HERE, 295 00:13:03,066 --> 00:13:05,533 WHAT YOU CAN SEE IS A WATERMELON-SHAPED CELL BODY 296 00:13:05,533 --> 00:13:08,800 AND PROCESSES THAT EXTEND OUT 297 00:13:08,800 --> 00:13:10,733 INTO THE MINERALIZED TISSUE. 298 00:13:10,733 --> 00:13:14,266 SO THESE CELLS FORM NETWORKS WITH OTHER OSTEOCYTES, 299 00:13:14,266 --> 00:13:18,133 AND THESE CELLS ARE THOUGHT TO SENSE THE MECHANICAL ENVIRONMENT 300 00:13:18,133 --> 00:13:21,233 IN TERMS OF MECHANICAL STRAIN, 301 00:13:21,233 --> 00:13:23,633 FLUID SHEAR STRESS, ACCELERATION. 302 00:13:23,633 --> 00:13:27,066 AND THESE CELLS ARE THOUGHT TO DIRECT BONE REMODELING. 303 00:13:28,933 --> 00:13:31,066 SO WE HAVE A SPECIAL PERFORMANCE NOW. 304 00:13:31,066 --> 00:13:34,700 BIOLOGY'S AN INHERENTLY COLLABORATIVE FIELD. 305 00:13:34,700 --> 00:13:38,000 AND SO TO ILLUSTRATE THIS PROCESS OF BONE REMODELING, 306 00:13:38,000 --> 00:13:42,033 WE HAVE AN ACTOR WHO'S-- ANN-SOFIE-- 307 00:13:42,033 --> 00:13:43,933 WHO'S AN ASTRONAUT. 308 00:13:43,933 --> 00:13:48,600 AND WE'RE GONNA DEMONSTRATE THE PROCESS OF BONE REMODELING. 309 00:13:48,600 --> 00:13:52,100 SO PLEASE WELCOME THE BONE AND SIGNALING LAB ACTING TROUPE. 310 00:13:52,100 --> 00:13:54,833 [cheers and applause] 311 00:13:57,900 --> 00:14:01,933 SO FIRST, WE'LL COVER BONE RESORPTION. 312 00:14:01,933 --> 00:14:05,466 SO OSTEOCYTES, WHICH-- [Pac-Man music] 313 00:14:05,466 --> 00:14:08,400 AH, WE HAVE A--WE HAVE A SIGNAL BEING SENT. 314 00:14:08,400 --> 00:14:10,966 [laughs] SO OSTEOCYTES, 315 00:14:10,966 --> 00:14:12,800 WHICH ARE THE CELLS THAT RESIDE WITHIN THE BONE, 316 00:14:12,800 --> 00:14:15,333 THEY SEND A MOLECULAR SIGNAL TO THE MARROW 317 00:14:15,333 --> 00:14:17,300 AND TO OSTEOCLAST PRECURSORS. 318 00:14:17,300 --> 00:14:19,433 THESE CELLS THEN HOME TO THE BONE SURFACE, 319 00:14:19,433 --> 00:14:22,533 ATTACH, AND DEPOSIT ACID 320 00:14:22,533 --> 00:14:24,700 AND ACTIVELY DEGRADE AWAY THE MATRIX 321 00:14:24,700 --> 00:14:26,233 AND THE MINERALIZED TISSUE. 322 00:14:26,233 --> 00:14:28,666 BY THAT MECHANISM, 323 00:14:28,666 --> 00:14:31,333 WE GET CHANGES IN STRUCTURAL VOLUME. 324 00:14:31,333 --> 00:14:34,233 NEXT, THE OTHER COMPONENT OF BONE REMODELING 325 00:14:34,233 --> 00:14:36,366 IS BONE FORMATION. 326 00:14:36,366 --> 00:14:38,600 SO AGAIN, WE HAVE A UNIQUE MOLECULAR SIGNAL 327 00:14:38,600 --> 00:14:41,566 SENT TO THE OSTEOBLAST PROGENITOR, 328 00:14:41,566 --> 00:14:43,533 WHICH THEN COMES TO THE BONES SURFACE 329 00:14:43,533 --> 00:14:45,866 AND CREATES NEW MATRIX AND NEW MINERAL. 330 00:14:45,866 --> 00:14:48,000 AND BY THAT--BY THIS PROCESS, THE COORDINATED ACT-- 331 00:14:48,000 --> 00:14:51,666 ACTIVITY OF THESE CELLS, WE HAVE FRESH NEW BONE 332 00:14:51,666 --> 00:14:53,400 AND SKELETAL HOMEOSTASIS. 333 00:14:53,400 --> 00:14:55,966 AND IN ASTRONAUTS, WE SEE THAT THESE PROCESSES GO AWRY. 334 00:14:55,966 --> 00:14:58,300 SO WITH THAT, PLEASE-- 335 00:14:58,300 --> 00:15:00,433 PLEASE THANK ANN-SOFIE AS THE ASTRONAUT. 336 00:15:00,433 --> 00:15:01,833 [applause] 337 00:15:01,833 --> 00:15:04,233 MOHIT, BETSABEL, AND REBECCA. 338 00:15:08,533 --> 00:15:10,700 [chuckles] 339 00:15:10,700 --> 00:15:13,066 I DEFINITELY OWE YOU ALL SOME BEERS AFTER THIS. 340 00:15:13,066 --> 00:15:15,066 [laughs] 341 00:15:18,900 --> 00:15:22,033 SO BUILDING ON THIS IDEA OF BONE IS A LIVING STRUCTURE 342 00:15:22,033 --> 00:15:23,766 AND THE PROCESS OF BONE REMODELING, 343 00:15:23,766 --> 00:15:26,033 IT'S NOT TOO FAR A LEAP TO STATE 344 00:15:26,033 --> 00:15:27,600 THAT BONE REMODELING IS A FUNCTION 345 00:15:27,600 --> 00:15:29,566 OF THE MECHANICAL LOADING ENVIRONMENT. 346 00:15:29,566 --> 00:15:32,800 AND SO IN MORE SPECIFICITY 347 00:15:32,800 --> 00:15:34,866 THE MECHANICAL STRAIN EXPERIENCED 348 00:15:34,866 --> 00:15:37,266 BY THE DEFORMATION OF THE BONE, 349 00:15:37,266 --> 00:15:40,100 FLUID SHEAR STRESS AS IT PASSES OVER THE SURFACE OF THE BONE, 350 00:15:40,100 --> 00:15:43,266 HYDROSTATIC PRESSURE, AND ALSO GRAVITY 351 00:15:43,266 --> 00:15:46,233 IN TERMS OF GRAVITATIONAL ACCELERATION. 352 00:15:46,233 --> 00:15:48,066 THESE ELEVATIONS IN MECHANICAL LOADING, 353 00:15:48,066 --> 00:15:51,200 WHEN THEY'RE ELEVATED, CAUSE, FOR EXAMPLE, 354 00:15:51,200 --> 00:15:54,366 DURING EXERCISE, CAUSE CHANGES IN BONE VOLUME. 355 00:15:54,366 --> 00:15:56,800 AND THIS IS THE DOMAIN OF THE OSTEOBLASTS. 356 00:15:56,800 --> 00:15:59,466 IN THE-- IN THE OPPOSITE DIRECTION, 357 00:15:59,466 --> 00:16:03,433 IN MICROGRAVITY, WEIGHTLESSNESS, AND BED REST, 358 00:16:03,433 --> 00:16:07,600 THIS IS IN THE DOMAIN OF THE OSTEOCLAST CELLS, 359 00:16:07,600 --> 00:16:11,866 AND SO WE SEE NEGATIVE CHANGES IN BONE VOLUME. 360 00:16:11,866 --> 00:16:13,800 TO ILLUSTRATE THESE IDEAS IN MORE DEPTH, 361 00:16:13,800 --> 00:16:17,133 WE'LL LOOK AT THE RIGHT AND LEFT ARM OF A TENNIS PLAYER 362 00:16:17,133 --> 00:16:19,866 AS A MODEL OF ELEVATED MECHANICAL LOADING. 363 00:16:19,866 --> 00:16:22,366 SO LOOKING AT THIS X-RAY, 364 00:16:22,366 --> 00:16:24,500 WHAT WE SEE IS THAT ELITE TENNIS PLAYERS 365 00:16:24,500 --> 00:16:26,433 WHO HAVE PLAYED THEIR WHOLE LIFE 366 00:16:26,433 --> 00:16:28,666 WITH HITTING--HITTING THE TENNIS BALL WITH ONE HAND, 367 00:16:28,666 --> 00:16:32,166 THEY HAVE--THEY SHOW, YOU KNOW, IMMEDIATE DIFFERENCES 368 00:16:32,166 --> 00:16:36,300 IN THE MINERAL DENSITY AND ALSO THE GEOMETRY 369 00:16:36,300 --> 00:16:38,033 OF--OF THEIR ARMS. 370 00:16:38,033 --> 00:16:42,500 AND SO THAT MANIFESTS IN BONE MINERAL CONTENT 371 00:16:42,500 --> 00:16:44,800 AS WELL AS DIAMETER 372 00:16:44,800 --> 00:16:46,366 AND THICKNESS OF THE BONE. 373 00:16:46,366 --> 00:16:50,366 AND UNDOUBTEDLY THESE GEOMETRIC AND MATERIAL CHANGES 374 00:16:50,366 --> 00:16:53,600 CAN IMPROVE STRENGTH AS WELL. 375 00:16:53,600 --> 00:16:56,666 IN CONTRAST, ASTRONAUTS EXPERIENCE WEIGHTLESSNESS 376 00:16:56,666 --> 00:16:58,366 DURING MICROGRAVITY. 377 00:16:58,366 --> 00:17:01,733 THIS DOESN'T MEAN INACTIVITY JUST DIFFERENT LOADING PROFILE 378 00:17:01,733 --> 00:17:03,266 THAN WHAT'S EXPERIENCED ON EARTH. 379 00:17:03,266 --> 00:17:05,533 AND SO WHAT THIS HISTOGRAM SHOWS 380 00:17:05,533 --> 00:17:08,366 IS THE NUMBER OF LOADING OCCURRENCES 381 00:17:08,366 --> 00:17:12,866 VERSUS THE--EACH PEAK FORCE OF EACH OCCURRENCE. 382 00:17:12,866 --> 00:17:16,166 AND SO IN BLACK, YOU SEE NORMAL ACTIVITY 383 00:17:16,166 --> 00:17:19,233 LIKE WALKING AND RUNNING 384 00:17:19,233 --> 00:17:20,966 ON 1G HERE ON EARTH. 385 00:17:20,966 --> 00:17:24,666 AND IN GRAY, YOU SEE THE INTERNATIONAL SPACE STATION. 386 00:17:24,666 --> 00:17:28,566 SO RUNNING ON THE COLD, BARE TREADMILL, FOR EXAMPLE, 387 00:17:28,566 --> 00:17:31,700 THAT GETS A PEAK FORCE OF ABOUT 1.4 388 00:17:31,700 --> 00:17:34,366 ON ISS, 1.4 TIMES BODY WEIGHT. 389 00:17:34,366 --> 00:17:37,100 WHEREAS ON EARTH, IT'S ABOUT 2.5. 390 00:17:37,100 --> 00:17:40,566 AND SO THIS IS--SUNI WILLIAMS, WHEN SHE RAN THE BOSTON MARATHON 391 00:17:40,566 --> 00:17:42,666 IN SPACE, SHE--SHE SAID 392 00:17:42,666 --> 00:17:46,300 THAT SHE WAS GETTING ABOUT 75 TO 85% OF HER BODY WEIGHT 393 00:17:46,300 --> 00:17:48,700 LOADING ON THE-- ON THE TREADMILL. 394 00:17:48,700 --> 00:17:51,066 APPARENTLY IT WASN'T DESIGNED TO DO MARATHONS IN SPACE, 395 00:17:51,066 --> 00:17:55,100 AND SO IT WAS VERY UNCOMFORTABLE TO RUN 26.2 MILES. 396 00:17:55,100 --> 00:17:58,933 INTERESTING NOTE, WHEN SHE RETURNED THE YEAR AFTER 397 00:17:58,933 --> 00:18:00,466 AND SHE RAN THE BOSTON MARATHON, 398 00:18:00,466 --> 00:18:03,966 SHE SHAVED ABOUT HALF AN HOUR OFF OF HER TIME. 399 00:18:03,966 --> 00:18:07,200 SO, YOU KNOW, YOU CAN IMMEDIATELY SEE 400 00:18:07,200 --> 00:18:11,133 THAT THE HIGH FORCE EXERCISE STIMULATION IS MISSING 401 00:18:11,133 --> 00:18:12,900 ON ISS. 402 00:18:12,900 --> 00:18:16,266 AND THIS WAS A GAP IN THE--IN THE CADRE OF EXERCISE EQUIPMENT 403 00:18:16,266 --> 00:18:17,966 FOR SOME TIME. 404 00:18:17,966 --> 00:18:19,966 AND THOUGH THIS HAS SINCE BEEN RECTIFIED, 405 00:18:19,966 --> 00:18:22,833 AND I'LL SHARE THOSE RESULTS WITH YOU IN A MOMENT. 406 00:18:22,833 --> 00:18:26,166 SO WHAT HAVE WE LEARNED FROM THE--FROM THE PAST DECADES 407 00:18:26,166 --> 00:18:27,900 OF RESEARCH INTO THIS AREA? 408 00:18:27,900 --> 00:18:29,800 SO THIS IS REALLY THE KEY DATA FROM ASTRONAUTS 409 00:18:29,800 --> 00:18:31,433 THAT CHARACTERIZE THE PROBLEM, 410 00:18:31,433 --> 00:18:33,300 AND THIS IS GENERATED THROUGH DEXA SCANS 411 00:18:33,300 --> 00:18:35,700 AND MORE RECENTLY THROUGH CT SCANS. 412 00:18:35,700 --> 00:18:38,566 SO--SO RIGHT HERE, IT'S SHOWN-- 413 00:18:38,566 --> 00:18:40,366 THIS IS DATA FROM MIR, 414 00:18:40,366 --> 00:18:44,200 AND SO WHAT YOU SEE IS THAT IN LONG-DURATION MISSIONS 415 00:18:44,200 --> 00:18:47,066 BONE LOSS MANIFESTS, AND IT APPEARS AT A RATE 416 00:18:47,066 --> 00:18:50,433 OF ABOUT 1% LOSS OF BONE MINERAL DENSITY PER MONTH. 417 00:18:50,433 --> 00:18:52,866 THIS OCCURS IN THE WEIGHT-BEARING BONES, 418 00:18:52,866 --> 00:18:55,566 LIKE THE SPINE, 419 00:18:55,566 --> 00:18:58,833 THE FEMORAL NECK, THE TIBIA. 420 00:18:58,833 --> 00:19:01,533 BUT IT DOESN'T MANIFEST IN THE UPPER EXTREMITIES, 421 00:19:01,533 --> 00:19:04,233 LIKE THE HUMERUS. 422 00:19:04,233 --> 00:19:06,900 SO THESE WEIGHT-BEARING BONES ARE REALLY-- 423 00:19:06,900 --> 00:19:09,433 THEY NEED THIS MECHANICAL FORCE TO SURVIVE 424 00:19:09,433 --> 00:19:12,533 AND TO MAINTAIN HOMEOSTASIS. 425 00:19:12,533 --> 00:19:15,700 IN MORE DEPTH, THE SKELETAL TURNOVER 426 00:19:15,700 --> 00:19:18,000 IS MORE PRONOUNCED IN THE CANCELLOUS TISSUE. 427 00:19:18,000 --> 00:19:20,600 AND ONCE THE ASTRONAUTS RETURN TO EARTH, 428 00:19:20,600 --> 00:19:23,266 IT TAKES A LONG TIME TO RECOVER. 429 00:19:23,266 --> 00:19:25,766 AND IN FACT, IT MAY NOT EVER RECOVER 430 00:19:25,766 --> 00:19:29,466 AFTER--AFTER ONE YEAR EARTHBOUND. 431 00:19:31,366 --> 00:19:35,666 AND AS A RESULT OF CANCELLOUS DEFICITS, 432 00:19:35,666 --> 00:19:37,566 THERE'S AN EXPANSION OF THE CORTICAL BONE 433 00:19:37,566 --> 00:19:39,433 THAT--THAT TAKES PLACE IN ASTRONAUTS 434 00:19:39,433 --> 00:19:41,566 AFTER THEY'VE RETURNED TO NORMAL LOADING. 435 00:19:43,166 --> 00:19:45,466 SO, YOU KNOW, TAKEN TOGETHER, 436 00:19:45,466 --> 00:19:47,766 I THINK THIS REALLY IS A CONCERN 437 00:19:47,766 --> 00:19:50,066 IN TERMS OF ASTRONAUT FRACTURE RISK. 438 00:19:52,233 --> 00:19:54,466 IN FACT, WE CAN QUANTIFY THIS RISK IN MORE DETAIL 439 00:19:54,466 --> 00:19:56,533 WITH COMPUTER MODELING. 440 00:19:56,533 --> 00:19:59,466 SO FROM THE IN VIVO CT SCANS 441 00:19:59,466 --> 00:20:01,166 FROM THE ASTRONAUT BONES, 442 00:20:01,166 --> 00:20:02,900 ONE CAN GENERATE STRUCTURAL ANALYSES-- 443 00:20:02,900 --> 00:20:04,900 IN THIS CASE, FINITE ELEMENTS-- 444 00:20:04,900 --> 00:20:07,400 AND INVESTIGATE THE DISTRIBUTION OF STRESS 445 00:20:07,400 --> 00:20:09,033 WITHIN BONES. 446 00:20:09,033 --> 00:20:11,800 AND SO THIS IS THE CONCENTRATION OF FORCE WITHIN AN AREA. 447 00:20:11,800 --> 00:20:14,833 THIS EXEMPLARY FIGURE SHOWS HIGH STRESS 448 00:20:14,833 --> 00:20:17,733 IN THE FEMORAL HEAD, 449 00:20:17,733 --> 00:20:19,600 WITH RED BEING HIGH SHEAR STRESS 450 00:20:19,600 --> 00:20:21,666 AND BLUE BEING LOW. 451 00:20:23,333 --> 00:20:26,000 AND SO THIS TYPE OF ANALYSIS 452 00:20:26,000 --> 00:20:28,266 WAS PERFORMED BEFORE AND AFTER FLIGHT 453 00:20:28,266 --> 00:20:29,833 ON ASTRONAUTS. 454 00:20:29,833 --> 00:20:31,900 AND SO THE DATA IS HERE ON THE LEFT 455 00:20:31,900 --> 00:20:35,400 WITH A STANCE LOADING CONFIGURATION 456 00:20:35,400 --> 00:20:37,500 AND A FALL LOADING CONFIGURATION. 457 00:20:37,500 --> 00:20:39,500 AND SO EACH LINE HERE IS AN INDEPENDENT ASTRONAUT 458 00:20:39,500 --> 00:20:41,633 BEFORE AND AFTER FLIGHT. 459 00:20:41,633 --> 00:20:45,000 AND SO ACROSS THE BOARD, YOU CAN SEE THERE'S A LARGE MAJORITY 460 00:20:45,000 --> 00:20:46,933 OF NEGATIVE SLOPES 461 00:20:46,933 --> 00:20:50,000 IN EACH LOADING CONFIGURATION. 462 00:20:50,000 --> 00:20:51,633 AND WITH THE STANCE CONFIGURATION, 463 00:20:51,633 --> 00:20:54,700 THERE'S ABOUT A 2.5% DECREMENT PER MONTH 464 00:20:54,700 --> 00:20:58,133 IN--IN THE BONE STRENGTH 465 00:20:58,133 --> 00:21:00,433 NORMALIZED PER BODY WEIGHT. 466 00:21:00,433 --> 00:21:02,866 AND THESE DATA SUGGEST THAT THE FORCES ARE CONCENTRATING 467 00:21:02,866 --> 00:21:05,300 WITHIN THE ASTRONAUT BONES 468 00:21:05,300 --> 00:21:08,400 AND SUGGEST ASTRONAUT BONES HAVE REDUCED STRENGTH. 469 00:21:10,433 --> 00:21:13,900 AND NOW, TRANSITIONING TO MODEL ORGANISMS 470 00:21:13,900 --> 00:21:15,200 THAT HAVE BEEN FLOWN INTO SPACE 471 00:21:15,200 --> 00:21:17,400 AS WELL AS GROUND-BASED MODELS 472 00:21:17,400 --> 00:21:19,333 THAT INCORPORATE MODEL ORGANISMS 473 00:21:19,333 --> 00:21:22,666 AND--AND HUMAN MODELS OF WEIGHTLESSNESS. 474 00:21:22,666 --> 00:21:25,933 IT'S--THESE TYPES OF ANALYSES 475 00:21:25,933 --> 00:21:27,933 COMPLEMENT THOSE PRIMARY DATA SETS 476 00:21:27,933 --> 00:21:30,766 THAT WE JUST WENT OVER FROM THE ASTRONAUTS. 477 00:21:32,133 --> 00:21:35,133 AND SO WE CAN COMPARE THE DATA THAT WE JUST REVIEWED 478 00:21:35,133 --> 00:21:36,900 AND ALSO EXTEND OUR UNDERSTANDING 479 00:21:36,900 --> 00:21:40,033 AND LOOK AT MORE FUNDAMENTAL BIOLOGY MECHANISMS, 480 00:21:40,033 --> 00:21:42,633 LOOK AT THE CELLULAR AND MOLECULAR CHANGES 481 00:21:42,633 --> 00:21:45,233 THAT THE ANIMALS OR THE HUMANS ARE EXPERIENCING. 482 00:21:45,233 --> 00:21:47,700 AND SO IN 1978, 483 00:21:47,700 --> 00:21:49,900 IT WAS OBSERVED WITH ANIMALS FLOWN IN SPACE 484 00:21:49,900 --> 00:21:51,533 THAT THERE WAS DECREASED MINERALIZATION 485 00:21:51,533 --> 00:21:53,733 BY OSTEOBLAST CELLS. 486 00:21:53,733 --> 00:21:58,633 MORE RECENTLY, THERE'S--IN A SIMULATION OF WEIGHTLESSNESS, 487 00:21:58,633 --> 00:22:00,333 SHOWN HERE-- 488 00:22:00,333 --> 00:22:02,133 THIS IS CALLED THE HINDLIMB UNLOADING MODEL 489 00:22:02,133 --> 00:22:04,133 OF--USED FOR RODENTS TO SIMULATE WEIGHTLESSNESS 490 00:22:04,133 --> 00:22:07,000 ON THE TIBIA AND FEMUR. 491 00:22:07,000 --> 00:22:09,766 THEY--THESE RESEARCHERS IDENTIFIED 492 00:22:09,766 --> 00:22:11,800 ELEVATED OSTEOCLAST ACTIVITY, 493 00:22:11,800 --> 00:22:14,000 AND THIS IS MOST LIKELY RESPONSIBLE 494 00:22:14,000 --> 00:22:17,566 FOR BONE LOSS OBSERVED IN SIMULATED WEIGHTLESSNESS. 495 00:22:17,566 --> 00:22:20,433 AND THERE'S--THIS DATA WAS ALSO CONFIRMED IN HUMANS 496 00:22:20,433 --> 00:22:22,233 WHO WERE UNDERGOING BED REST. 497 00:22:22,233 --> 00:22:24,300 SO 12 WEEKS OF BED REST 498 00:22:24,300 --> 00:22:26,766 LISTED ELEVATIONS IN OSTEOCLAST ACTIVITY 499 00:22:26,766 --> 00:22:29,666 AND DECREASES IN OSTEOBLAST ACTIVITY. 500 00:22:29,666 --> 00:22:31,933 SO THESE--THINKING BACK TO THE BONE REMODELING, 501 00:22:31,933 --> 00:22:35,733 THESE ARE ALL REALLY NEGATIVE FOR-- 502 00:22:35,733 --> 00:22:38,700 FOR SKELETAL STRUCTURE AND-- 503 00:22:38,700 --> 00:22:41,366 AND THIS PROVIDES CELLULAR MECHANISMS 504 00:22:41,366 --> 00:22:43,700 THAT UNDERLIE THOSE VOLUMETRIC CHANGES. 505 00:22:45,733 --> 00:22:47,433 WITH ANIMALS FLOWN IN SPACE, 506 00:22:47,433 --> 00:22:50,533 WE CAN OBSERVE THE SKELETON WITH GREATER RESOLUTION. 507 00:22:50,533 --> 00:22:53,500 AND SO WHAT'S SHOWN HERE ARE THE PELVIC ISCHIA 508 00:22:53,500 --> 00:22:55,966 OF GROUND CONTROL ON THE LEFT 509 00:22:55,966 --> 00:22:58,666 AND 15 DAYS OF SPACEFLIGHT ON THE RIGHT. 510 00:22:58,666 --> 00:23:00,966 THESE WERE IMAGED WITH MICRO-CT BY COLLEAGUES 511 00:23:00,966 --> 00:23:03,333 IN THE BONE AND SIGNALING LAB HERE AT AMES. 512 00:23:03,333 --> 00:23:05,566 AND WHAT THESE SHOW 513 00:23:05,566 --> 00:23:08,000 IS THAT BONE LOSS OCCURRED IN THE PELVIC AREA 514 00:23:08,000 --> 00:23:10,300 THROUGH THINNING OF THE CORTICAL BONE. 515 00:23:10,300 --> 00:23:12,100 AND IN OTHER--IN THE FEMUR, 516 00:23:12,100 --> 00:23:15,400 IT ACTUALLY SHOWED THINNING OF BOTH THE CORTEX 517 00:23:15,400 --> 00:23:17,533 AS WELL AS THE TRABECULAR STRUTS. 518 00:23:19,266 --> 00:23:21,033 AND WHAT-- 519 00:23:21,033 --> 00:23:23,133 SO THIS IS A TRABECULAR STRUT ON THE RIGHT. 520 00:23:23,133 --> 00:23:25,933 AND SO BASICALLY JUST A RADIAL DECREASE 521 00:23:25,933 --> 00:23:28,266 IN--IN THAT STRUCTURE. 522 00:23:28,266 --> 00:23:31,633 AND THEN IN COMPLEMENTARY GROUND-BASED MODELS 523 00:23:31,633 --> 00:23:33,833 THIS SHOWS PROGRESSIVE THINNING 524 00:23:33,833 --> 00:23:36,766 AND EVENTUALLY REMOVAL OF THESE TRABECULAE 525 00:23:36,766 --> 00:23:39,633 WITH--WITH LONGER DURATION SPACEFLIGHT. 526 00:23:39,633 --> 00:23:42,933 SO IT'S THE PROGRESSION OVER THE COURSE OF A COUPLE MONTHS, 527 00:23:42,933 --> 00:23:44,433 OR WEEKS TO MONTHS, 528 00:23:44,433 --> 00:23:47,400 THAT THE SURFACE MEDIATED RESORPTION 529 00:23:47,400 --> 00:23:51,366 STARTS TO REMOVE AWAY THESE TRABECULAR STRUTS. 530 00:23:51,366 --> 00:23:53,333 AND ONCE THEY'RE REMOVED, 531 00:23:53,333 --> 00:23:55,866 THEY CANNOT BE CREATED DE NOVO. 532 00:23:55,866 --> 00:23:58,200 SO THAT'S--THIS UNDERSCORES 533 00:23:58,200 --> 00:24:00,266 KIND OF A STRUCTURAL MECHANISM 534 00:24:00,266 --> 00:24:02,900 UNDERLYING THESE REALLY PERSISTENT DEFICITS 535 00:24:02,900 --> 00:24:04,766 IN THE ASTRONAUT CANCELLOUS TISSUE 536 00:24:04,766 --> 00:24:06,966 AND WHY THE CORTICAL BONE 537 00:24:06,966 --> 00:24:09,400 SEEMS TO COMPENSATE WITH AN EXPANSION. 538 00:24:11,466 --> 00:24:15,233 ADDITIONALLY, BONES FROM SPACEFLIGHT ANIMALS 539 00:24:15,233 --> 00:24:17,233 AND GROUND-BASED MODELS HAVE CONFIRMED 540 00:24:17,233 --> 00:24:20,500 THAT MECHANICAL PROPERTIES AND BONE STRENGTH ARE REDUCED 541 00:24:20,500 --> 00:24:24,100 FOLLOWING WEIGHTLESSNESS. 542 00:24:24,100 --> 00:24:25,866 WITHIN THESE SAME MICE WE ASKED, 543 00:24:25,866 --> 00:24:28,166 HOW ARE THE OSTEOCYTES RESPONDING? 544 00:24:28,166 --> 00:24:30,100 WE ANALYZED THE SPACE-FLOWN BONES 545 00:24:30,100 --> 00:24:32,000 AT SLAC NATIONAL LAB 546 00:24:32,000 --> 00:24:35,833 WITH A 30 NANOMETER X-RAY TRANSITION MICROSCOPE-- 547 00:24:35,833 --> 00:24:37,500 TRANSMISSION MICROSCOPE. 548 00:24:37,500 --> 00:24:39,033 AND SO THESE IMAGES ARE PICTURED HERE. 549 00:24:39,033 --> 00:24:40,966 THE GROUND CONTROL ON THE LEFT 550 00:24:40,966 --> 00:24:43,266 AND THE SPACE-FLOWN ANIMALS ON THE RIGHT. 551 00:24:43,266 --> 00:24:45,600 AND WE ASKED WHETHER THE LOCAL TISSUE DENSITY 552 00:24:45,600 --> 00:24:47,466 WAS ALTERED DURING SPACEFLIGHT, 553 00:24:47,466 --> 00:24:49,266 AND WHETHER THE OSTEOCYTES SHOWED 554 00:24:49,266 --> 00:24:51,300 ANY MORPHOLOGICAL CHANGES, 555 00:24:51,300 --> 00:24:53,500 AND THE RESULTS WERE SURPRISING. 556 00:24:53,500 --> 00:24:56,133 WE DID NOT SEE ANY TISSUE LEVEL DENSITY CHANGES, 557 00:24:56,133 --> 00:24:58,333 BUT WE DID SEE THE LACUNAE-- 558 00:24:58,333 --> 00:25:01,133 THESE ARE THE APARTMENTS OF THE OSTEOCYTES-- 559 00:25:01,133 --> 00:25:04,066 THESE WERE BECOMING LARGER 560 00:25:04,066 --> 00:25:06,700 IN TERMS OF THEIR AREA AND PERIMETER. 561 00:25:06,700 --> 00:25:10,033 AND THESE DATA SUGGEST AN ADDITIONAL METHOD 562 00:25:10,033 --> 00:25:12,033 OF BONE REMODELING 563 00:25:12,033 --> 00:25:14,933 IN ADDITION TO THE SURFACE MEDIATED OSTEOCLAST RESORPTION. 564 00:25:14,933 --> 00:25:18,200 NAMELY, THESE BONES ARE REMODELING FROM THE INSIDE OUT. 565 00:25:18,200 --> 00:25:21,100 AND COLLEAGUES IN THE BONE AND SIGNALING LAB CONFIRMED 566 00:25:21,100 --> 00:25:24,366 THIS REMODELING PHENOTYPE 567 00:25:24,366 --> 00:25:26,966 WITH PROTEIN MARKERS OF MATRIX 568 00:25:26,966 --> 00:25:30,100 AND MINERAL REMODELING WITHIN THE OSTEOCYTE LACUNAE. 569 00:25:32,833 --> 00:25:34,733 SO STEPPING BACK TO ASTRONAUTS 570 00:25:34,733 --> 00:25:38,100 AND INTRODUCING THE IDEA OF EXERCISE AS A COUNTERMEASURE, 571 00:25:38,100 --> 00:25:41,233 RECALL THAT THE LACK OF HIGH-FORCE EXERCISES 572 00:25:41,233 --> 00:25:43,900 COULD BE A CRITICAL WEAKNESS 573 00:25:43,900 --> 00:25:48,066 OF UNDERLYING THE BONE LOSS THAT WE TALKED ABOUT EARLIER. 574 00:25:48,066 --> 00:25:50,433 AND THIS RELATIVELY NEW DEVICE, 575 00:25:50,433 --> 00:25:53,300 THE ADVANCED RESISTIVE EXERCISE DEVICE 576 00:25:53,300 --> 00:25:55,166 PICTURED HERE, 577 00:25:55,166 --> 00:25:57,066 HAS BECOME THE FIRST EFFECTIVE COUNTERMEASURE 578 00:25:57,066 --> 00:25:59,900 AT PREVENTING BONE LOSS EXPERIENCED BY ASTRONAUTS. 579 00:25:59,900 --> 00:26:03,166 SO WITH THIS DEVICE, THEY CAN GET ABOUT 500 POUNDS OF FORCE 580 00:26:03,166 --> 00:26:04,966 IN A SQUAT EXERCISE. 581 00:26:04,966 --> 00:26:07,233 THEY CAN DO HEEL RAISES 582 00:26:07,233 --> 00:26:09,966 AND REALLY REINTRODUCE 583 00:26:09,966 --> 00:26:12,766 THIS--THIS HIGH-FORCE EXERCISE ONTO THE WEIGHT-BEARING BONES. 584 00:26:12,766 --> 00:26:15,133 AND WHAT THE DATA SUGGESTS 585 00:26:15,133 --> 00:26:17,433 ARE IN THE SPINE AND THE FEMUR 586 00:26:17,433 --> 00:26:19,700 AND THE PELVIS, THAT THIS IS PREVENTING 587 00:26:19,700 --> 00:26:22,700 THAT--THE BONE LOSS THAT WE TALKED ABOUT EARLIER. 588 00:26:22,700 --> 00:26:25,133 HOWEVER, WE'RE NOT OUT OF THE WOODS YET. 589 00:26:25,133 --> 00:26:27,700 WHEN YOU LOOK AT THE BLOOD AND THE URINE, 590 00:26:27,700 --> 00:26:29,600 THE SKELETON IS IN A HIGH-TURNOVER STATE. 591 00:26:29,600 --> 00:26:32,066 SO WHAT THAT MEANS IS FORMATION IS HIGH, 592 00:26:32,066 --> 00:26:34,366 WHICH IS A GOOD THING, BUT RESORPTION IS STILL HIGH. 593 00:26:34,366 --> 00:26:37,633 SO THE OSTEOCLASTS ARE STILL IN AN ACTIVE STATE. 594 00:26:37,633 --> 00:26:40,166 SO I DON'T THINK WE'VE FULLY SOLVED THE PROBLEM, 595 00:26:40,166 --> 00:26:42,900 AND WE DON'T KNOW AT WHAT QUALITY THE BONE IS 596 00:26:42,900 --> 00:26:45,766 THAT FORMS UNDER THIS HIGH-TURNOVER STATE. 597 00:26:45,766 --> 00:26:49,500 NONETHELESS, THIS IS THE FIRST EFFECTIVE COUNTERMEASURE 598 00:26:49,500 --> 00:26:52,266 THAT--THAT--TO PREVENT BONE LOSS IN SPACE. 599 00:26:54,466 --> 00:26:57,233 LESS WELL-KNOWN ARE THE EFFECTS OF SPACE RADIATION 600 00:26:57,233 --> 00:26:58,966 ON THE BODY AND ON THE SKELETON, 601 00:26:58,966 --> 00:27:02,666 AND AS THE EARTH MAGNETIC FIELD IS CURRENTLY SHIELDING 602 00:27:02,666 --> 00:27:04,933 MOST OF THE CHARGED PARTICLE FLUX. 603 00:27:04,933 --> 00:27:07,600 THE RAD DOSIMETER, WHICH SHOWED-- 604 00:27:07,600 --> 00:27:09,700 WHICH TOOK DATA ON THE CRUISE PHASE TO MARS 605 00:27:09,700 --> 00:27:12,300 WITH THE "CURIOSITY" ROVER 606 00:27:12,300 --> 00:27:16,300 HAS MEASURED THE DOSE RATES OF THE GALACTIC COSMIC RADIATION, 607 00:27:16,300 --> 00:27:20,200 WHICH IS THIS LOW CHRONIC EXPOSURE 608 00:27:20,200 --> 00:27:21,933 THAT ASTRONAUTS WOULD BE EXPERIENCING, 609 00:27:21,933 --> 00:27:24,033 AS WELL AS SOLAR PARTICLE EVENTS-- 610 00:27:24,033 --> 00:27:27,000 THESE LITTLE SPIKES IN THE DOSE RATE 611 00:27:27,000 --> 00:27:29,200 VERSUS TIME CHART HERE. 612 00:27:29,200 --> 00:27:32,600 AND THE GCR PARTICLES ARE REALLY THE ONES OF CONCERN. 613 00:27:32,600 --> 00:27:35,033 THE--THEY'RE REALLY HARD TO SHIELD, 614 00:27:35,033 --> 00:27:37,866 AND THEY CAN DO REALLY INTENSE DAMAGE. 615 00:27:37,866 --> 00:27:42,833 AND THAT'S SHOWN HERE IN A PROTEIN--IN GREEN HERE, 616 00:27:42,833 --> 00:27:46,500 THAT LABELS ACTIVE DNA DAMAGE REPAIR OCCURRING. 617 00:27:46,500 --> 00:27:49,200 AND SO AT DOSES HERE THAT ARE ACHIEVABLE 618 00:27:49,200 --> 00:27:51,400 DURING A MARS-- A ROUND-TRIP MARS MISSION, 619 00:27:51,400 --> 00:27:54,900 YOU CAN SEE THAT THESE TYPES OF EXPOSURES 620 00:27:54,900 --> 00:27:57,433 ARE ELICITING DNA DAMAGE 621 00:27:57,433 --> 00:27:58,900 AND IN ADDITION, 622 00:27:58,900 --> 00:28:02,466 THEY CAN ELICIT FREE RADICAL STRESS TO ORGANISMS. 623 00:28:04,033 --> 00:28:06,733 AND SO DURING MY POSTDOCTORAL FELLOWSHIP, 624 00:28:06,733 --> 00:28:08,833 WE AIMED TO BETTER QUANTIFY THE EFFECTS 625 00:28:08,833 --> 00:28:11,566 OF SPACE RADIATION ON THE SKELETAL TISSUE. 626 00:28:14,600 --> 00:28:18,300 AND SO TO SIMULATE SPACE RADIATION, IONS AND ENERGIES, 627 00:28:18,300 --> 00:28:20,766 WE WENT TO THE NASA SPACE RADIATION LAB 628 00:28:20,766 --> 00:28:23,700 AT BROOKHAVEN NATIONAL LAB IN LONG ISLAND 629 00:28:23,700 --> 00:28:26,500 WERE WE USED A GAMMA RADIATION SOURCE. 630 00:28:26,500 --> 00:28:28,533 AND WE FOUND THAT RADIATION EXPOSURE 631 00:28:28,533 --> 00:28:31,266 CAUSES RAPID AND IRREVERSIBLE BONE LOSS. 632 00:28:31,266 --> 00:28:33,866 AND THINKING OF THE CANCELLOUS TISSUE, 633 00:28:33,866 --> 00:28:38,200 THIS WAS AFFECTED BY REMOVAL OF THE CANCELLOUS STRUTS. 634 00:28:38,200 --> 00:28:40,666 SO THIS IS A SIMILAR PROGRESSIVE BONE LOSS 635 00:28:40,666 --> 00:28:43,266 BUT IT--AS SIMULATED WEIGHTLESSNESS 636 00:28:43,266 --> 00:28:45,466 OR SPACEFLIGHT, 637 00:28:45,466 --> 00:28:49,233 BUT IT JUST HAPPENS MUCH, MUCH MORE RAPIDLY. 638 00:28:49,233 --> 00:28:52,166 AND SO THIS IS ATTRIBUTED TO THE OSTEOCLAST CELLS. 639 00:28:52,166 --> 00:28:55,766 THEY'RE MORE IN NUMBER. THEY'RE GREATER IN SIZE. 640 00:28:55,766 --> 00:28:58,600 AND THIS PERSISTED 641 00:28:58,600 --> 00:29:01,900 UNTIL--UNTIL AGE-RELATED BONE LOSS 642 00:29:01,900 --> 00:29:04,666 OVERTOOK THAT STRUCTURAL DECREMENT. 643 00:29:04,666 --> 00:29:07,033 SO WHAT'S SHOWN HERE IN BLACK IS-- 644 00:29:07,033 --> 00:29:09,333 CHARACTERIZES AGE-RELATED BONE LOSS OVER-- 645 00:29:09,333 --> 00:29:12,333 IN A MOUSE OVER A PERIOD OF ABOUT FOUR MONTHS. 646 00:29:12,333 --> 00:29:15,700 AND YOU CAN SEE THE REMOVAL OF TRABECULAR STRUTS 647 00:29:15,700 --> 00:29:18,466 REDUCING THIS PARAMETER CALLED TRABECULAR NUMBER, 648 00:29:18,466 --> 00:29:20,633 AND THEN THAT--THIS TISSUE NEVER RECOVERS. 649 00:29:20,633 --> 00:29:23,100 IT JUST GETS OVERTAKEN BY AGE-RELATED BONE LOSS. 650 00:29:25,633 --> 00:29:28,500 FURTHER, WE-- 651 00:29:28,500 --> 00:29:30,333 WE PERFORMED FINE ELEMENT MODELING 652 00:29:30,333 --> 00:29:32,000 ON THE VERTEBRA 653 00:29:32,000 --> 00:29:34,166 FROM SPECIMENS THAT HAD BEEN IRRADIATED 654 00:29:34,166 --> 00:29:37,366 AND EXPERIENCED THIS TYPE OF REMOVAL OF TRABECULAR STRUTS. 655 00:29:37,366 --> 00:29:40,400 AND WHAT WE SAW WAS THAT THE STRESS IN THESE BONES 656 00:29:40,400 --> 00:29:42,433 CONCENTRATES WITHIN THE REMAINING TISSUE 657 00:29:42,433 --> 00:29:44,233 ON THE CANCELLOUS BONE. 658 00:29:44,233 --> 00:29:46,900 ALSO, BECAUSE OF THE REMOVAL OF THESE LOAD PATHS, 659 00:29:46,900 --> 00:29:49,566 THERE'S MORE STRESS ON THE SURROUNDING CORTICAL SHELL. 660 00:29:49,566 --> 00:29:51,566 SO THIS IS--THIS IS-- 661 00:29:51,566 --> 00:29:54,500 THIS IS A REAL RISK FOR ASTRONAUT BONE STRENGTH 662 00:29:54,500 --> 00:29:57,466 ONCE THEY REACH THIS RADIATION DOSE. 663 00:29:59,666 --> 00:30:02,600 I'D LIKE TO KIND OF TAPER DOWN THE TALK 664 00:30:02,600 --> 00:30:04,100 AT THE MOLECULAR LEVEL 665 00:30:04,100 --> 00:30:06,766 AND THIS IS THE REALM OF PROTEINS, 666 00:30:06,766 --> 00:30:08,800 RECEPTORS, AND LIGANDS. 667 00:30:08,800 --> 00:30:10,833 THESE ARE CELL MACHINERY 668 00:30:10,833 --> 00:30:13,000 THAT ENGAGE WITH CELLS-- 669 00:30:13,000 --> 00:30:15,166 ALLOW THEM TO ENGAGE WITH THE ENVIRONMENT 670 00:30:15,166 --> 00:30:16,733 IN TRANSDUCED MECHANICAL SIGNALS 671 00:30:16,733 --> 00:30:19,600 AND ALSO TO COMMUNICATE WITH NEIGHBORING CELLS. 672 00:30:19,600 --> 00:30:21,866 SO WE DEMONSTRATED EARLIER 673 00:30:21,866 --> 00:30:24,600 THAT OSTEOCYTES CONTROL BONE REMODELING 674 00:30:24,600 --> 00:30:27,500 HOWEVER, THE SIGNALING MOLECULES 675 00:30:27,500 --> 00:30:29,400 THAT ELICIT THESE-- THIS CONTROL 676 00:30:29,400 --> 00:30:32,366 HAVE BEEN FAIRLY RECENTLY DISCOVERED 677 00:30:32,366 --> 00:30:34,200 IN THE PAST 15 YEARS OR SO. 678 00:30:34,200 --> 00:30:36,200 AND SO WE ASKED-- WELL, THE FIELD ASKED, 679 00:30:36,200 --> 00:30:39,066 HOW DO THESE MOLECULES CHANGE DURING SIMULATED SPACEFLIGHT? 680 00:30:39,066 --> 00:30:41,766 AND SO THERE ARE THREE KEY SIGNALING MOLECULES 681 00:30:41,766 --> 00:30:43,000 THAT I'LL TALK ABOUT TODAY. 682 00:30:43,000 --> 00:30:45,233 THE FIRST IS SCLEROSTIN. 683 00:30:45,233 --> 00:30:48,266 THIS IS A UNIQUE PROTEIN THAT OSTEOCYTES PRODUCE 684 00:30:48,266 --> 00:30:52,766 AND SECRETE INTO THE EXTRA CELLULAR SPACE. 685 00:30:52,766 --> 00:30:56,933 AND THIS SCLEROSTIN INHIBITS BONE FORMATION, 686 00:30:56,933 --> 00:30:58,900 AND SO THUS, IT ESTABLISHES NEGATIVE FEEDBACK 687 00:30:58,900 --> 00:31:01,400 WITHIN THIS OSTEOBLAST LINEAGE, 688 00:31:01,400 --> 00:31:03,400 WHERE HIGHER SCLEROSTIN LEVELS 689 00:31:03,400 --> 00:31:05,600 CAUSE LESS BONE FORMATION. 690 00:31:07,233 --> 00:31:10,200 THE NEXT MOLECULAR SIGNAL IS RANK LIGAND. 691 00:31:10,200 --> 00:31:14,533 AND THIS IS A LIGAND NOT UNIQUE TO OSTEOCYTES, 692 00:31:14,533 --> 00:31:17,433 HOWEVER THIS IS AN IMPORTANT FACTOR 693 00:31:17,433 --> 00:31:19,700 FOR DRIVING OSTEOCLAST FORMATION 694 00:31:19,700 --> 00:31:22,966 AND INITIATING THE PROCESS OF BONE RESORPTION. 695 00:31:22,966 --> 00:31:25,866 THERE'S A THIRD PLAYER 696 00:31:25,866 --> 00:31:27,966 NAMED OSTEOPROTEGERIN, 697 00:31:27,966 --> 00:31:30,900 WHICH IS OPG, SECRETED BY OSTEOCYTES 698 00:31:30,900 --> 00:31:32,766 AND OTHER CELLS 699 00:31:32,766 --> 00:31:35,600 THAT INHIBITS THIS RANK LIGAND MOLECULE. 700 00:31:35,600 --> 00:31:38,200 AND SO THIS STARTS TO-- 701 00:31:38,200 --> 00:31:41,433 IF THESE ARE IMPLICATED IN SPACEFLIGHT-INDUCED BONE LOSS, 702 00:31:41,433 --> 00:31:43,466 THEN THESE PROTEINS BECOME TRANSLATIONAL TARGETS 703 00:31:43,466 --> 00:31:45,366 FOR OUR COUNTERMEASURE DEVELOPMENT. 704 00:31:47,233 --> 00:31:50,166 NOW, RECALL THAT BONE FORMATION IS LOW IN SPACEFLIGHT. 705 00:31:50,166 --> 00:31:54,433 AND SIMULATIONS OF MICROGRAVITY 706 00:31:54,433 --> 00:31:57,733 HAVE SHOWN THAT SCLEROSTIN LEVELS ARE HIGH 707 00:31:57,733 --> 00:32:00,766 IN BED REST AND IN HINDLIMB UNLOADING MODELS. 708 00:32:00,766 --> 00:32:03,666 OPPOSITELY, PHYSIOLOGIC LOADING, 709 00:32:03,666 --> 00:32:07,233 LIKE EXERCISE OR PRESCRIBED MECHANICAL FORCE, 710 00:32:07,233 --> 00:32:09,466 DECREASE THESE SCLEROSTIN LEVELS 711 00:32:09,466 --> 00:32:13,433 AND NEGATIVELY REGULATE BONE FORMATION. 712 00:32:13,433 --> 00:32:15,966 SO TAKEN TOGETHER, INHIBITING SCLEROSTIN 713 00:32:15,966 --> 00:32:19,166 SHOULD RESTORE BONE FORMATION IN ASTRONAUTS. 714 00:32:19,166 --> 00:32:22,266 AND THIS IDEA WAS SHOWN TO BE CORRECT 715 00:32:22,266 --> 00:32:24,166 IN A SIMULATION OF WEIGHTLESSNESS. 716 00:32:24,166 --> 00:32:27,733 AND SO WHAT THEY DID WAS HINDLIMB UNLOAD ANIMALS 717 00:32:27,733 --> 00:32:30,333 AND TREAT THEM WITH AN ANTIBODY 718 00:32:30,333 --> 00:32:32,833 FOR THIS SCLEROSTIN MOLECULE, 719 00:32:32,833 --> 00:32:35,866 NEUTRALIZING THE ACTIVITY OF THAT MOLECULE. 720 00:32:35,866 --> 00:32:39,400 AND THIS WAS SHOWN TO STIMULATE BONE FORMATION 721 00:32:39,400 --> 00:32:41,400 IN THE CANCELLOUS TISSUE AND THE CORTICAL TISSUE 722 00:32:41,400 --> 00:32:44,366 AND PREVENT THE NEGATIVE CONSEQUENCES 723 00:32:44,366 --> 00:32:48,100 OF CONCENTRATING STRESS, SHOWN HERE IN RED, 724 00:32:48,100 --> 00:32:51,766 THAT WEIGHTLESSNESS AFFECTS. 725 00:32:51,766 --> 00:32:55,266 FURTHER, THIS ANTIBODY WAS TESTED ON STS-135, 726 00:32:55,266 --> 00:32:58,033 AND RESULTS ARE STILL FORTHCOMING. 727 00:32:58,033 --> 00:33:00,966 THIS MOLECULE-- THIS ANTIBODY TREATMENT 728 00:33:00,966 --> 00:33:03,533 IS CURRENTLY UNDERGOING CLINICAL TRIALS 729 00:33:03,533 --> 00:33:07,000 FOR OSTEOPOROSIS TREATMENT. 730 00:33:07,000 --> 00:33:09,700 SO THIS IS ONE LEVER OF MOLECULAR CONTROL 731 00:33:09,700 --> 00:33:11,966 OF BONE FORMATION THAT COULD HELP ASTRONAUTS 732 00:33:11,966 --> 00:33:14,033 PROTECT THEIR SKELETAL STRUCTURE. 733 00:33:15,800 --> 00:33:17,900 MOVING TO BONE RESORPTION, 734 00:33:17,900 --> 00:33:19,666 RECALL THAT IT'S HIGH IN SPACEFLIGHT. 735 00:33:19,666 --> 00:33:22,200 AND IN SIMULATIONS OF WEIGHTLESSNESS, 736 00:33:22,200 --> 00:33:25,433 IT'S BEEN SHOWN THAT RANK LIGAND EXPRESSION IS ELEVATED. 737 00:33:25,433 --> 00:33:29,100 ADDITIONALLY, AFTER HIGH DOSES OF RADIATION, 738 00:33:29,100 --> 00:33:31,966 RANK LIGAND IS ALSO ELEVATED, 739 00:33:31,966 --> 00:33:34,400 AS IS BONE RESORPTION. 740 00:33:34,400 --> 00:33:36,666 AND WE'RE ACTIVELY INVESTIGATING WHETHER RANK LIGAND 741 00:33:36,666 --> 00:33:39,566 PLAYS A ROLE IN THE RESPONSE TO SPACE RADIATION EXPOSURE. 742 00:33:41,333 --> 00:33:43,000 SO THIS INFORMATION SUGGESTS RANK LIGAND 743 00:33:43,000 --> 00:33:45,500 IS DRIVING OSTEOCLAST FORMATION 744 00:33:45,500 --> 00:33:47,800 AND BONE FORMATION IN ASTRONAUTS, 745 00:33:47,800 --> 00:33:50,900 AND RESEARCHERS HAVE ASKED, 746 00:33:50,900 --> 00:33:52,900 WHAT ROLE DO OSTEOCYTES PLAY 747 00:33:52,900 --> 00:33:56,200 IN CREATING RANK LIGAND? 748 00:33:56,200 --> 00:33:59,200 AND ADDITIONALLY, BECAUSE RANK LIGAND IS A KEY PLAYER, 749 00:33:59,200 --> 00:34:01,500 THAT INHIBITOR OF RANK LIGAND, 750 00:34:01,500 --> 00:34:05,333 OPG, COULD BE A TRANSLATIONAL-- 751 00:34:05,333 --> 00:34:07,333 A COUNTERMEASURE FOR ASTRONAUTS. 752 00:34:08,966 --> 00:34:11,033 SO TO IDENTIFY THE CELLULAR SOURCE 753 00:34:11,033 --> 00:34:12,733 OF THIS RANK LIGAND, 754 00:34:12,733 --> 00:34:14,933 A GROUP OUT OF LITTLE ROCK 755 00:34:14,933 --> 00:34:17,400 CREATED A TRANSGENIC MOUSE MODEL 756 00:34:17,400 --> 00:34:19,700 THAT DELETED THE RANK LIGAND GENE 757 00:34:19,700 --> 00:34:22,400 UNIQUELY IN OSTEOCYTE CELLS. 758 00:34:22,400 --> 00:34:26,000 AND THIS IS THE DMP1-CRE PROMOTER 759 00:34:26,000 --> 00:34:27,633 HERE ON THE RIGHT. 760 00:34:27,633 --> 00:34:29,633 SO WHAT THEIR EXPERIMENT SHOWS 761 00:34:29,633 --> 00:34:32,000 IS THAT, AS EXPECTED, 762 00:34:32,000 --> 00:34:34,366 THE SIMULATED WEIGHTLESSNESS CAUSES BONE LOSS, 763 00:34:34,366 --> 00:34:40,166 HOWEVER, IN THE DELETED-- THE OSTEOCYTE-SPECIFIC DELETION 764 00:34:40,166 --> 00:34:43,400 ANIMALS WERE NOT LOSING BONE. 765 00:34:43,400 --> 00:34:46,300 AND SO THIS IS SAYING THAT, ONE, 766 00:34:46,300 --> 00:34:48,566 THAT THE OSTEOCYTES ARE PRODUCING THE RANK LIGAND, 767 00:34:48,566 --> 00:34:51,100 AND THAT THIS IS THE RESPONSIBLE MECHANISM 768 00:34:51,100 --> 00:34:53,933 FOR WEIGHTLESSNESS-INDUCED BONE LOSS. 769 00:34:57,633 --> 00:35:01,400 LOOKING NEXT AT OPG 770 00:35:01,400 --> 00:35:05,066 AND A FAMILY OF MOLECULES CALLED ANTIRESORPTIVES, 771 00:35:05,066 --> 00:35:07,633 IT'S BEEN--LONG BEEN KNOWN 772 00:35:07,633 --> 00:35:09,833 THAT BISPHOSPHONATES ARE AN FDA APPROVED DRUG 773 00:35:09,833 --> 00:35:11,466 FOR OSTEOPOROSIS, 774 00:35:11,466 --> 00:35:13,866 AND THEY PREVENT OSTEOCLAST ATTACHMENT 775 00:35:13,866 --> 00:35:16,466 AND PREVENT OSTEOCLAST SURVIVAL. 776 00:35:16,466 --> 00:35:19,166 AND THEY HAVE BEEN TESTED IN ASTRONAUTS, 777 00:35:19,166 --> 00:35:22,766 AND THIS IS SHOWN TO PREVENT THE SPACEFLIGHT-INDUCED BONE LOSS. 778 00:35:22,766 --> 00:35:24,600 SO THIS IS THE SECOND COUNTERMEASURE 779 00:35:24,600 --> 00:35:26,500 THAT IS IN OUR TOOLBOX 780 00:35:26,500 --> 00:35:29,033 TO PREVENT THESE NEGATIVE CHANGES IN THE SKELETON. 781 00:35:29,033 --> 00:35:33,200 IN MICE, THIS FAMILY OF DRUGS, BISPHOSPHONATES, 782 00:35:33,200 --> 00:35:35,766 ALSO PREVENTED RADIATION-INDUCED BONE LOSS. 783 00:35:37,666 --> 00:35:39,500 AND LOOKING AT OPG, 784 00:35:39,500 --> 00:35:41,500 BASICALLY INHIBITING THAT RANK LIGAND MOLECULE, 785 00:35:41,500 --> 00:35:44,900 THIS--IN MICE, THIS WAS SHOWN IN STS-108, 786 00:35:44,900 --> 00:35:48,633 THAT IT PREVENTED SPACEFLIGHT-INDUCED BONE LOSS. 787 00:35:48,633 --> 00:35:52,066 SO THIS IS ALL FINE AND GOOD, 788 00:35:52,066 --> 00:35:53,933 BUT THERE'S STILL A NEGATIVE SIDE EFFECT 789 00:35:53,933 --> 00:35:56,600 OF PROLONGED USE OF SOME OF THESE ANTIRESORPTIVES. 790 00:35:56,600 --> 00:35:59,400 AND THIS HAS SHOWN UP IN OSTEOPOROTIC PATIENTS. 791 00:35:59,400 --> 00:36:01,566 THERE'S UNCOUPLING OF BONE REMODELING, 792 00:36:01,566 --> 00:36:03,333 WHICH YOU ALL UNDERSTAND NOW, 793 00:36:03,333 --> 00:36:05,966 BUT THERE'S ALSO OSTEONECROSIS OF THE JAW 794 00:36:05,966 --> 00:36:07,833 AND FEMORAL FRACTURES THAT ARE ATYPICAL 795 00:36:07,833 --> 00:36:09,466 EMERGED WITH PROLONGED USE. 796 00:36:09,466 --> 00:36:12,233 SO I THINK THESE ANTIRESORPTIVES ARE GOOD FOR THE SHORT DURATION, 797 00:36:12,233 --> 00:36:14,266 BUT NOT--THEY'RE NOT A PERMANENT SOLUTION. 798 00:36:16,300 --> 00:36:20,100 SO IN SUMMARY, WE'VE REALLY JUST SCRATCHED THE SURFACE TODAY, 799 00:36:20,100 --> 00:36:22,033 BUT THESE ARE BY NO MEANS 800 00:36:22,033 --> 00:36:24,100 THE ONLY SIGNALING MOLECULES OF RELEVANCE. 801 00:36:24,100 --> 00:36:25,633 BUT I HOPE THAT I'VE SUCCEEDED IN COMMUNICATING 802 00:36:25,633 --> 00:36:29,600 THE VALUE AND IMPORTANCE OF SPACE BIOLOGY 803 00:36:29,600 --> 00:36:32,500 AND STUDYING BONE LOSS IN ASTRONAUTS. 804 00:36:32,500 --> 00:36:35,600 I THINK WE'VE ILLUSTRATED THIS PROCESS OF DISCOVERY 805 00:36:35,600 --> 00:36:39,133 AND BRINGING SOLUTIONS 806 00:36:39,133 --> 00:36:41,600 TO THE ASTRONAUT. 807 00:36:41,600 --> 00:36:44,900 SO I'D LIKE TO CLOSE WITH JUST A SNAPSHOT OF WHERE WE'RE GOING. 808 00:36:44,900 --> 00:36:47,766 AND THIS IS A SLIDE THAT JEFF SMITH PROVIDED ME. 809 00:36:47,766 --> 00:36:50,466 THIS IS A--IT'S A PLOT OF DISTANCE THAT WE'VE TRAVELED 810 00:36:50,466 --> 00:36:53,366 FROM EARTH VERSUS THE MISSION DURATION. 811 00:36:53,366 --> 00:36:55,333 AND WHAT YOU SEE IS-- 812 00:36:55,333 --> 00:36:57,933 THIS L-SHAPE IN THE LOWER LEFT, 813 00:36:57,933 --> 00:37:00,466 THIS IS WHERE WE'VE BEEN SO FAR, 814 00:37:00,466 --> 00:37:03,733 AND THIS BIG ELLIPSE IS WHERE WE WANNA GO. 815 00:37:03,733 --> 00:37:05,666 AND I THINK-- 816 00:37:05,666 --> 00:37:07,900 I THINK WE CAN USE MODEL ORGANISMS 817 00:37:07,900 --> 00:37:10,000 AND A BASIC BIOLOGY APPROACH 818 00:37:10,000 --> 00:37:12,733 TO REALLY HELP ENABLE REACHING OUT 819 00:37:12,733 --> 00:37:15,933 AND EXTENDING DURATION AND EXTENDING DISTANCE 820 00:37:15,933 --> 00:37:18,233 FROM--FROM EARTH. 821 00:37:18,233 --> 00:37:20,933 SO WITH THAT, I THANK YOU FOR YOUR ATTENTION 822 00:37:20,933 --> 00:37:23,333 AND YOUR ATTENDANCE TODAY 823 00:37:23,333 --> 00:37:26,000 AND OPEN IT UP FOR QUESTIONS. 824 00:37:26,000 --> 00:37:29,000 [applause] 825 00:37:40,566 --> 00:37:43,066 - HI. I HAVE A QUESTION IN REGARDS 826 00:37:43,066 --> 00:37:46,000 TO THE AGE OF THE SUBJECTS THAT YOU WERE LOOKING AT. 827 00:37:46,000 --> 00:37:48,133 ARE THESE ALL YOUNG MICE OR OLDER MICE 828 00:37:48,133 --> 00:37:50,466 OR HAVE YOU STUDIED DIFFERENT AGE GROUPS? 829 00:37:50,466 --> 00:37:52,033 - THERE HAVE BEEN-- 830 00:37:52,033 --> 00:37:54,133 I THINK THE ORIGINAL STUDIES WERE WITH GROWING RATS. 831 00:37:54,133 --> 00:37:56,766 BUT THESE--I THINK THOSE 832 00:37:56,766 --> 00:37:58,966 ARE VERY KEENLY TUNED 833 00:37:58,966 --> 00:38:02,033 TO THE MECHANICAL ENVIRONMENT 834 00:38:02,033 --> 00:38:04,833 AND THOSE--THOSE SHOWED THE FIRST NEGATIVE CHANGES 835 00:38:04,833 --> 00:38:06,433 IN THE OSTEOBLAST. 836 00:38:06,433 --> 00:38:08,300 HOWEVER, WITH ADULT ANIMALS, 837 00:38:08,300 --> 00:38:10,766 I THINK YOU SEE SOMETHING MAYBE NOT AS DRAMATIC 838 00:38:10,766 --> 00:38:12,966 BUT SOMETHING IN THE SAME DIRECTION. 839 00:38:15,866 --> 00:38:18,166 OH, AND ALSO THE HUMAN BONE BIOPSY 840 00:38:18,166 --> 00:38:21,000 ALSO ACTUALLY SHOWED-- THESE WERE ADULT HUMANS, 841 00:38:21,000 --> 00:38:23,666 AND THAT SHOWED NEGATIVE OSTEOBLAST CHANGES AS WELL. 842 00:38:25,100 --> 00:38:27,033 - FIRST, THANKS FOR PUTTING AN O'NEILL CYLINDER 843 00:38:27,033 --> 00:38:29,166 ON YOUR SLIDES. THAT WAS NICE. 844 00:38:29,166 --> 00:38:31,466 I HAVE A QUESTION ABOUT CALCULATING THE-- 845 00:38:31,466 --> 00:38:34,400 THE BIOLOGICAL EFFECTIVENESS FOR GCR. 846 00:38:34,400 --> 00:38:36,266 - MM-HMM. - I THINK, 847 00:38:36,266 --> 00:38:38,266 ALTHOUGH I MIGHT BE WRONG, THAT ALMOST ALL THE DATA 848 00:38:38,266 --> 00:38:41,900 IS FROM A FAIRLY SHORT DURATION AND A LITTLE HIGHER DOSES 849 00:38:41,900 --> 00:38:45,066 BUT YOU NEED TO UNDERSTAND WHAT LOW DOSES 850 00:38:45,066 --> 00:38:47,000 OVER LONG PERIODS OF TIME, AND HOW-- 851 00:38:47,000 --> 00:38:49,366 IS THAT CONVERSION MADE IN SOME AD HOC WAY, 852 00:38:49,366 --> 00:38:51,733 OR IS THERE SOMETHING REALLY SOLID THAT DOES IT? 853 00:38:51,733 --> 00:38:53,166 - THAT'S--THAT'S A TOUGH QUESTION. 854 00:38:53,166 --> 00:38:55,633 I THINK--I THINK IT'S ON A TISSUE BY TISSUE BASIS. 855 00:38:55,633 --> 00:38:58,700 AND SO--AND IT DEPENDS ON WHAT YOU'RE MEASURING. 856 00:38:58,700 --> 00:39:00,800 ARE YOU GONNA MEASURE CELL DEATH? 857 00:39:00,800 --> 00:39:02,833 ARE YOU GONNA MEASURE FREE RADICAL GENERATION 858 00:39:02,833 --> 00:39:04,333 OR DNA DAMAGE? 859 00:39:04,333 --> 00:39:06,133 AND SO I THINK EACH OF THOSE-- WHATEVER YOU MEASURE 860 00:39:06,133 --> 00:39:07,600 IS GONNA HAVE A DIFFERENT 861 00:39:07,600 --> 00:39:09,200 RELATIVE BIOLOGICAL EFFECTIVENESS. 862 00:39:09,200 --> 00:39:11,000 I THINK MOST OF THE NUMBERS USED RIGHT NOW 863 00:39:11,000 --> 00:39:13,633 ARE FROM CELL DEATH OR EFFECTIVE CELL KILLING. 864 00:39:13,633 --> 00:39:15,666 - IS THAT HOW IT'S DONE FOR BONE? 865 00:39:15,666 --> 00:39:17,400 - MM-HMM. 866 00:39:20,300 --> 00:39:23,533 - HI, JOSH. ON ONE OF YOUR SLIDES, 867 00:39:23,533 --> 00:39:26,900 YOU SHOWED THE SPACEFLIGHT DATA FROM ASTRONAUTS, 868 00:39:26,900 --> 00:39:29,066 THAT THEY LOSE ABOUT 1% PER MONTH 869 00:39:29,066 --> 00:39:31,100 FOR THEIR WEIGHT-BEARING BONES 870 00:39:31,100 --> 00:39:33,566 BUT NOT FOR THE BONES OF THE UPPER EXTREMITIES. 871 00:39:33,566 --> 00:39:35,833 I'M CURIOUS WHAT YOU KNOW ABOUT THE MECHANISMS 872 00:39:35,833 --> 00:39:37,733 BY WHICH, YOU KNOW, YOUR ARM BONES 873 00:39:37,733 --> 00:39:41,133 ARE ABLE TO MAINTAIN HOMEOSTASIS, 874 00:39:41,133 --> 00:39:43,833 YOU KNOW, REGARDLESS OF GRAVITY LOAD, 875 00:39:43,833 --> 00:39:47,066 AND IF THAT CAN OFFER ANY INSIGHTS 876 00:39:47,066 --> 00:39:49,633 TO, YOU KNOW, HOW YOU CAN MANAGE BONE REMODELING 877 00:39:49,633 --> 00:39:51,433 IN MICROGRAVITY. 878 00:39:51,433 --> 00:39:52,766 I GUESS THE LAST PART IS, 879 00:39:52,766 --> 00:39:54,700 IS THAT PATTERN ALSO REFLECTED 880 00:39:54,700 --> 00:39:57,300 IN NORMAL OSTEOPOROTIC DISEASE PROCESSES 881 00:39:57,300 --> 00:39:59,600 FOR PATIENTS ON EARTH? 882 00:39:59,600 --> 00:40:02,100 - SO THE FIRST PART OF THE QUESTION, 883 00:40:02,100 --> 00:40:04,266 WE--I'VE NEVER LOOKED AT THAT, SO THAT'S A GOOD QUESTION. 884 00:40:04,266 --> 00:40:07,400 I WOULD PREDICT THAT IT UTILIZES SOME OF THE SAME MOLECULES 885 00:40:07,400 --> 00:40:10,266 TO REGULATE BONE TURNOVER, 886 00:40:10,266 --> 00:40:14,200 AND SO WE SAW WITH THIS USE IN THE BED REST, 887 00:40:14,200 --> 00:40:16,366 THE SCLEROSTIN WAS UP. 888 00:40:16,366 --> 00:40:20,000 AND SO I THINK THERE ARE A COUPLE INTERPRETATIONS. 889 00:40:20,000 --> 00:40:23,066 PERHAPS THE BONE IS AT A LOWER RATE OF TURNOVER TO BEGIN WITH, 890 00:40:23,066 --> 00:40:25,933 AND SO ANY CHANGE WOULD TAKE LONGER TO MANIFEST. 891 00:40:25,933 --> 00:40:28,766 OR THE SCLEROSTIN LEVEL VARIES BY TISSUE. 892 00:40:28,766 --> 00:40:31,866 AND MAYBE THAT HELPS EXPLAIN WHY 893 00:40:31,866 --> 00:40:35,933 THERE'S NOT A PHENOTYPE IN THE UPPER EXTREMITY. 894 00:40:35,933 --> 00:40:38,300 AND THE SECOND QUESTION, CAN YOU REPEAT? 895 00:40:38,300 --> 00:40:41,000 - WELL, COULD THAT-- 896 00:40:41,000 --> 00:40:44,266 IS THAT ALSO THE CASE FOR OSTEOPOROSIS ON EARTH? 897 00:40:44,266 --> 00:40:46,633 IS THERE A PATTERN BETWEEN LOAD-BEARING 898 00:40:46,633 --> 00:40:49,233 AND UNLOAD-BEARING BONES? 899 00:40:49,233 --> 00:40:51,666 - I THINK OSTEOPOROSIS ON EARTH, 900 00:40:51,666 --> 00:40:54,100 THERE'S A COUPLE DIFFERENT FORMS OF THE DISEASE. 901 00:40:54,100 --> 00:40:56,700 AND HORMONES PLAY AN IMPORTANT ROLE 902 00:40:56,700 --> 00:41:00,200 IN POSTMENOPAUSAL OSTEOPOROSIS. 903 00:41:00,200 --> 00:41:02,400 AND SO I THINK THERE ARE OTHER PLAYERS, 904 00:41:02,400 --> 00:41:05,100 BUT I THINK RANK LIGAND, SCLEROSTIN 905 00:41:05,100 --> 00:41:07,566 PROBABLY PLAY A ROLE. 906 00:41:10,600 --> 00:41:12,666 - HI. I WANT TO TOUCH ON A COUPLE DEEPER TOPICS 907 00:41:12,666 --> 00:41:14,566 THAT WE MAY HAVE TO HAVE BEERS ABOUT. 908 00:41:14,566 --> 00:41:17,100 BUT, UM... 909 00:41:17,100 --> 00:41:20,600 SO FIRST, COUNTER TO A LOT OF INTUITION, 910 00:41:20,600 --> 00:41:22,266 EVERYTHING I UNDERSTAND ABOUT BONE DEVELOPMENT 911 00:41:22,266 --> 00:41:24,300 IS THAT, FOR INSTANCE, COMPRESSION-- 912 00:41:24,300 --> 00:41:26,600 COMPRESSIVE PRESSURE ON A BONE 913 00:41:26,600 --> 00:41:29,600 CAUSES THAT BONE TO DEGRADE AND DISAPPEAR, 914 00:41:29,600 --> 00:41:32,033 VERSUS TENSION ON A BONE 915 00:41:32,033 --> 00:41:34,766 WILL CAUSE IT TO GROW, LIKE A BONE SPUR. 916 00:41:34,766 --> 00:41:38,166 SO THIS TIES IN TO SORT OF A DEEPER STORY 917 00:41:38,166 --> 00:41:40,800 OF, FOR INSTANCE, 918 00:41:40,800 --> 00:41:42,900 WHEN WE THINK OF "WEIGHT-BEARING" SKELETON, 919 00:41:42,900 --> 00:41:44,966 IT'S NOT ACTUALLY BECAUSE THE SKELETON IS BEING COMPRESSED 920 00:41:44,966 --> 00:41:46,566 BY THE WEIGHT OF THE BODY, 921 00:41:46,566 --> 00:41:49,633 IT'S BECAUSE IT'S EXPERIENCING GREATER TENSILE LOADS 922 00:41:49,633 --> 00:41:52,700 FROM THE MUSCLES SURROUNDING THEM. 923 00:41:52,700 --> 00:41:55,033 AND, UM... 924 00:41:55,033 --> 00:41:57,100 PART OF A SORT OF TENSION NETWORK APPROACH 925 00:41:57,100 --> 00:41:58,633 TO UNDERSTANDING THE BODY. 926 00:41:58,633 --> 00:42:00,633 IT'S A VERY DIFFERENT APPROACH THAN SORT OF COMMON SENSE, 927 00:42:00,633 --> 00:42:02,500 BUT THERE'S A LOT OF EVIDENCE BACKING IT. 928 00:42:02,500 --> 00:42:04,800 AND SO THAT WOULD FIT IN TO THIS IDEA 929 00:42:04,800 --> 00:42:07,433 THAT WHILE-- WHEN IN SPACEFLIGHT 930 00:42:07,433 --> 00:42:09,300 YOU ARE USING YOUR ARMS A LOT. 931 00:42:09,300 --> 00:42:10,966 YOU STILL NEED TO USE MUSCULAR ACTIVITY 932 00:42:10,966 --> 00:42:13,766 TO MOVE THE MASS AND INERTIA OF OBJECTS AROUND, 933 00:42:13,766 --> 00:42:16,300 AND ASTRONAUTS PUSH THEMSELVES AROUND A LOT WITH THEIR ARMS. 934 00:42:16,300 --> 00:42:18,333 SO THOSE MUSCLES ARE ACTIVE, THEREFORE THOSE BONES 935 00:42:18,333 --> 00:42:20,933 ARE GETTING LOTS OF LOAD AND SO THEY DON'T DEGRADE. 936 00:42:20,933 --> 00:42:23,766 WHEREAS THE LEGS AND OTHER PARTS OF THE BODY 937 00:42:23,766 --> 00:42:25,633 WHICH ARE ACCUSTOMED TO DEALING WITH GRAVITY AREN'T, 938 00:42:25,633 --> 00:42:27,933 THEREFORE THEY ARE NOT EXPERIENCING THAT SAME LEVEL 939 00:42:27,933 --> 00:42:29,666 OF TENSION. 940 00:42:29,666 --> 00:42:32,100 SO IT'S REALLY THE TENSION OF THE MUSCLES THAT'S THE ISSUE, 941 00:42:32,100 --> 00:42:34,466 NOT THE WEIGHT-BEARING, PER SE. 942 00:42:34,466 --> 00:42:36,500 - YEAH. I THINK-- 943 00:42:36,500 --> 00:42:39,833 YOU KNOW, A STATIC COMPRESSION CAN CERTAINLY BE DAMAGING 944 00:42:39,833 --> 00:42:41,466 INTO SKELETAL TISSUE, 945 00:42:41,466 --> 00:42:43,400 BUT YOU KNOW, INTERMITTENT COMPRESSION 946 00:42:43,400 --> 00:42:45,700 IS REALLY POSITIVE FOR SKELETAL GROWTH. 947 00:42:45,700 --> 00:42:47,900 SO I THINK--YOU KNOW, I THINK THE SKELETON IS SENSITIVE 948 00:42:47,900 --> 00:42:49,700 TO DIFFERENT TYPES OF FORCE. 949 00:42:49,700 --> 00:42:53,533 IT'S SENSITIVE TO TENSION, SHEAR, INTERMITTENT COMPRESSION. 950 00:42:53,533 --> 00:42:56,300 SO I THINK ALL THESE THINGS WOULD FEED INTO 951 00:42:56,300 --> 00:42:58,266 A PRETTY UNIQUE MODEL. 952 00:42:58,266 --> 00:43:01,866 BUT CERTAINLY, YOU'RE REMOVING THIS CONSTANT COMPRESSION 953 00:43:01,866 --> 00:43:04,266 OF WEIGHT-BEARING, 954 00:43:04,266 --> 00:43:06,300 SO I THINK THAT'S-- THAT'S A GOOD POINT. 955 00:43:06,300 --> 00:43:09,233 - AND HAVE PEOPLE LOOKED AT THE IDEA 956 00:43:09,233 --> 00:43:12,366 OF CONTINUOUS RESISTIVE DEVICES? 957 00:43:12,366 --> 00:43:14,266 FOR INSTANCE, I'VE BEEN TALKING WITH SOME FOLKS ABOUT, 958 00:43:14,266 --> 00:43:16,133 FOR INSTANCE, MAKING INFLATABLE EXOSKELETONS 959 00:43:16,133 --> 00:43:18,066 THAT ASTRONAUTS COULD WEAR ON A DAILY BASIS 960 00:43:18,066 --> 00:43:20,233 THAT WOULD RESIST ALL ACTIVITY AND ALL DIRECTIONS 961 00:43:20,233 --> 00:43:22,533 AND THEREFORE APPLY CONTINUAL LOADING? 962 00:43:22,533 --> 00:43:24,366 - YEAH, I THINK IT'S AN INTERESTING IDEA. 963 00:43:24,366 --> 00:43:26,900 THE KEY THING FROM THE HISTOGRAM CHART 964 00:43:26,900 --> 00:43:28,900 IS THAT YOU'D REALLY NEED 965 00:43:28,900 --> 00:43:31,333 TO GET UP TO THAT TWO AND THREE BODY WEIGHT 966 00:43:31,333 --> 00:43:32,800 HIGH-FORCE EXERCISE. 967 00:43:32,800 --> 00:43:34,866 AND SO IF YOU COULD HAVE A DEVICE THAT'S ABLE TO GET 968 00:43:34,866 --> 00:43:38,033 THAT FORCE REGIMEN, THEN YOU'RE GONNA BE SOME REALLY POTENT 969 00:43:38,033 --> 00:43:41,233 STIMULATION FOR BONE. - OKAY. 970 00:43:53,366 --> 00:43:56,166 - QUITE A FEW IMPLANT MANUFACTURERS 971 00:43:56,166 --> 00:43:59,200 ARE SUFFERING FROM THE SAME KIND OF PROBLEMS 972 00:43:59,200 --> 00:44:02,300 AS THE--YOU DESCRIBE THE BONE WE SAW. 973 00:44:02,300 --> 00:44:05,600 SO FOR EXAMPLE, IF WE INSTALL A FULLY NEW HIP 974 00:44:05,600 --> 00:44:07,000 FOR A PATIENT, 975 00:44:07,000 --> 00:44:09,866 THE LOWER PARTS OF THE-- 976 00:44:09,866 --> 00:44:13,800 OF THE FEMUR BONE ARE GOING TO START DEGRADING. 977 00:44:13,800 --> 00:44:16,233 HAVE YOU HAD ANY COLLABORATION 978 00:44:16,233 --> 00:44:18,733 WITH IMPLANT MANUFACTURERS OR HOSPITALS 979 00:44:18,733 --> 00:44:20,666 REGARDS OF THIS? 980 00:44:20,666 --> 00:44:22,300 - WE HAVE NOT. WE HAVE NOT. 981 00:44:22,300 --> 00:44:24,533 I MEAN, IT'S AN ACTIVE AREA OF RESEARCH IN THE FIELD, 982 00:44:24,533 --> 00:44:28,100 BUT WE'VE NOT DONE ANY DIRECT RESEARCH. 983 00:44:31,933 --> 00:44:34,766 - SO IF YOU COULD PLEASE JOIN ME IN THANKING JOSH ALWOOD. 984 00:44:34,766 --> 00:44:37,766 [applause]