1 00:00:10,600 --> 00:00:13,960 Speaker 1: Hi, it's os Voloshin here. Welcome to tech Stuff. This week, 2 00:00:14,000 --> 00:00:16,840 Speaker 1: we're taking a break from our usual Wednesday episode to 3 00:00:16,880 --> 00:00:19,560 Speaker 1: share the first episode of an exciting new podcast from 4 00:00:19,600 --> 00:00:24,520 Speaker 1: Kaleidoscope and iHeart Podcasts called On Crisper, The Story of 5 00:00:24,600 --> 00:00:28,400 Speaker 1: Jennifer Dowdner with Walter Isaacston. It's a five part series 6 00:00:28,400 --> 00:00:31,680 Speaker 1: that tells the story of Dowdner, a Nobel Prize winning 7 00:00:31,720 --> 00:00:36,080 Speaker 1: scientist who co created the revolutionary gene editing tool known 8 00:00:36,159 --> 00:00:40,159 Speaker 1: as Crisper. From the first whispers of genetically edited babies 9 00:00:40,200 --> 00:00:44,000 Speaker 1: in China to life saving treatments for rare diseases, On 10 00:00:44,159 --> 00:00:48,680 Speaker 1: Crisper explores the promise, peril, and ethical dilemmas of a 11 00:00:48,760 --> 00:00:54,720 Speaker 1: technology powerful enough to rewrite human destiny. The series traces 12 00:00:54,760 --> 00:00:59,240 Speaker 1: the intense global competition, personal stakes, and moral questions that 13 00:00:59,360 --> 00:01:04,280 Speaker 1: define the new frontier in synthetic biology, what Isaacson calls 14 00:01:04,600 --> 00:01:08,760 Speaker 1: the third great revolution of modern times. I've loved listening 15 00:01:08,800 --> 00:01:10,960 Speaker 1: to this show, and I hope you will as well. 16 00:01:11,120 --> 00:01:13,840 Speaker 1: If you do enjoy this first episode, please make sure 17 00:01:13,880 --> 00:01:15,919 Speaker 1: to find the rest of the series on your favorite 18 00:01:15,959 --> 00:01:19,120 Speaker 1: podcast app and subscribe to get new episodes in your feed. 19 00:01:19,280 --> 00:01:23,200 Speaker 1: Automatically every Tuesday. As for tech stuff, We'll see you 20 00:01:23,240 --> 00:01:24,759 Speaker 1: on Friday for the Week in Tech. 21 00:01:25,800 --> 00:01:28,399 Speaker 2: Last year, in Philadelphia, the mother and father of a 22 00:01:28,440 --> 00:01:32,399 Speaker 2: baby boy experienced any newborn parents' nightmare. They discovered that 23 00:01:32,440 --> 00:01:35,360 Speaker 2: their son, kJ had been born with a rare genetic 24 00:01:35,400 --> 00:01:39,160 Speaker 2: disease called urea cycle disorder, causing him to have abnormally 25 00:01:39,240 --> 00:01:43,320 Speaker 2: high levels of ammonia in his blood. The prognosis was devastating, 26 00:01:43,680 --> 00:01:46,600 Speaker 2: and the only conventional life saving treatment option was a 27 00:01:46,640 --> 00:01:49,640 Speaker 2: liver transplant, a treatment that kJ might not be able 28 00:01:49,720 --> 00:01:54,640 Speaker 2: to obtain or survive. But then a pair of doctors 29 00:01:54,640 --> 00:01:58,280 Speaker 2: at the Children's Hospital in Philadelphia approached Kj's family to 30 00:01:58,280 --> 00:02:00,840 Speaker 2: discuss the possibility of trying a treatment that had never 31 00:02:00,880 --> 00:02:03,840 Speaker 2: been tried before. They would try using a technology called 32 00:02:03,920 --> 00:02:07,720 Speaker 2: Crisper to correct the specific genetic flaws that were creating 33 00:02:07,760 --> 00:02:08,600 Speaker 2: Kj's condition. 34 00:02:09,760 --> 00:02:13,560 Speaker 3: So it takes about six months and the doctors developed 35 00:02:13,560 --> 00:02:19,720 Speaker 3: a drug that was designed to target baby Kj's genetic variant, 36 00:02:20,200 --> 00:02:25,560 Speaker 3: specifically targeted to that one letter mess up in his DNA. 37 00:02:26,400 --> 00:02:29,320 Speaker 3: In just a few days after his first injection, kJ 38 00:02:29,520 --> 00:02:33,480 Speaker 3: starts showing signs of improvement. It's totally miraculous. The color 39 00:02:33,520 --> 00:02:36,360 Speaker 3: returns to his cheeks, and for the first time he 40 00:02:36,440 --> 00:02:41,080 Speaker 3: can tolerate protein in his diet. His parents are overwhelmed. 41 00:02:41,639 --> 00:02:45,080 Speaker 3: After two months, the doctors described him as growing and 42 00:02:45,240 --> 00:02:48,480 Speaker 3: thriving with no side effects from the treatment, and with 43 00:02:48,560 --> 00:02:52,519 Speaker 3: every month the hope has grown that the world's first 44 00:02:53,120 --> 00:03:00,760 Speaker 3: personalized gene editing treatment has been a complete success. Now 45 00:03:00,760 --> 00:03:04,680 Speaker 3: you may think that therapy was developed over six months, 46 00:03:04,960 --> 00:03:08,000 Speaker 3: but it was actually the product of like thirty years 47 00:03:08,120 --> 00:03:11,120 Speaker 3: of biological research. I mean, there was a lot of 48 00:03:11,200 --> 00:03:14,720 Speaker 3: technological development that went into this, and their race to 49 00:03:14,880 --> 00:03:17,880 Speaker 3: arrive at this moment is just a great story of 50 00:03:17,919 --> 00:03:23,280 Speaker 3: ambition and competition and collaboration and triumph because the work 51 00:03:23,480 --> 00:03:27,720 Speaker 3: and the results are extraordinary, and much of it was 52 00:03:27,800 --> 00:03:33,400 Speaker 3: fueled by the quiet determination of a biochemist named Jennifer Dowdner. 53 00:03:33,880 --> 00:03:35,520 Speaker 3: And while that name may not be at the tip 54 00:03:35,520 --> 00:03:37,800 Speaker 3: of your tongue like Elon Musk or Steve Jobs or 55 00:03:37,800 --> 00:03:41,280 Speaker 3: maybe Benjamin Franklin, her work might be the thing that 56 00:03:41,360 --> 00:03:45,160 Speaker 3: saves your family like a different kJ or maybe it 57 00:03:45,280 --> 00:03:52,800 Speaker 3: already did, like with the COVID vaccine. 58 00:03:56,800 --> 00:03:59,840 Speaker 4: You know, we've never had in the past the ability 59 00:04:00,160 --> 00:04:04,760 Speaker 4: to change the fundamental chemical nature of who we are 60 00:04:05,160 --> 00:04:08,080 Speaker 4: in this way right and now we do and what 61 00:04:08,120 --> 00:04:08,680 Speaker 4: do we do with that? 62 00:04:12,040 --> 00:04:16,000 Speaker 3: The discovery is both a tale of pure curiosity driven 63 00:04:16,080 --> 00:04:20,080 Speaker 3: basic science as well as functional science. 64 00:04:21,600 --> 00:04:23,680 Speaker 2: This is the third time I've sat down with Isaacson 65 00:04:23,960 --> 00:04:26,880 Speaker 2: as part of an ongoing conversation we're having about his subjects, 66 00:04:27,240 --> 00:04:28,880 Speaker 2: the kind of people who changed the world by the 67 00:04:28,880 --> 00:04:31,719 Speaker 2: force of their intellect. In the first season, we talked 68 00:04:31,760 --> 00:04:35,520 Speaker 2: about Elon Musk and Isaacson's six hundred page biography of him, 69 00:04:35,839 --> 00:04:38,600 Speaker 2: the tone that launched a thousand hot takes. In our 70 00:04:38,640 --> 00:04:42,440 Speaker 2: second we focused on a less polarizing inventor, Benjamin Franklin, 71 00:04:42,600 --> 00:04:44,760 Speaker 2: whose life in thinking helped us make sense of today's 72 00:04:44,760 --> 00:04:48,239 Speaker 2: turbulent times. The origins of our third sit down traced 73 00:04:48,279 --> 00:04:51,160 Speaker 2: back to twenty twelve, when the world first heard about 74 00:04:51,160 --> 00:04:54,240 Speaker 2: a new gene editing tool called Crisper. A breakthrough that 75 00:04:54,279 --> 00:04:57,240 Speaker 2: would allow us to modify our own genes, copying and 76 00:04:57,279 --> 00:05:00,840 Speaker 2: pasting them like a sentence. ISAC's and when he learned 77 00:05:00,839 --> 00:05:03,600 Speaker 2: the news, saw it as something more than a singular invention. 78 00:05:04,480 --> 00:05:07,520 Speaker 2: To him, it represented, as he's written, the beginning of 79 00:05:07,560 --> 00:05:10,680 Speaker 2: the third great Revolution of modern times, followed by the 80 00:05:10,720 --> 00:05:13,320 Speaker 2: revolutions in physics and information technology. 81 00:05:14,000 --> 00:05:16,599 Speaker 3: I was trying to create a pantheon of books about 82 00:05:16,680 --> 00:05:21,599 Speaker 3: great geniuses and the scientific revolutions. They were creating Einstein, 83 00:05:21,640 --> 00:05:24,600 Speaker 3: who brings us into the atomic era, of Steve Jobs, 84 00:05:24,640 --> 00:05:28,400 Speaker 3: who brought us into the digital age, but also we're 85 00:05:28,560 --> 00:05:33,680 Speaker 3: entering an age of a life sciences revolution, and I 86 00:05:33,800 --> 00:05:39,159 Speaker 3: wanted to find somebody who represented this revolution. He was 87 00:05:39,200 --> 00:05:43,800 Speaker 3: this brilliant, understated person, this woman who wasn't macurial or 88 00:05:43,839 --> 00:05:48,359 Speaker 3: cantankerous like Steve Jobs or Elon Musk, but was quietly 89 00:05:48,520 --> 00:05:51,839 Speaker 3: leading a revolution. She wasn't just cloning sheep. She was 90 00:05:51,960 --> 00:05:57,120 Speaker 3: pushing through technologies at are life changing. And I thought, hey, 91 00:05:57,360 --> 00:05:58,960 Speaker 3: I need to spend time with her. 92 00:06:01,760 --> 00:06:05,240 Speaker 2: I'm Evan rightlift. And this is on Crisper. The Story 93 00:06:05,279 --> 00:06:18,400 Speaker 2: of Jennifer Dowdner, Episode one, Beginnings for Isaacson. The Tale 94 00:06:18,400 --> 00:06:21,440 Speaker 2: of how Jennifer Dowdner delivered Crisper has its deepest roots 95 00:06:21,440 --> 00:06:23,640 Speaker 2: in her childhood in Hilo, Hawaii. 96 00:06:25,440 --> 00:06:29,760 Speaker 3: She's in Hawaii and she's looking at things like sleeping grass. Well, 97 00:06:29,760 --> 00:06:33,400 Speaker 3: if you touch it, it curls up. I remember that. 98 00:06:33,480 --> 00:06:36,719 Speaker 3: I remember touching farnes. They curl up, But I didn't 99 00:06:36,760 --> 00:06:40,400 Speaker 3: sit there and obsess like, how does the leaf know 100 00:06:40,480 --> 00:06:43,839 Speaker 3: how to do? It? Does have a motor inside, what 101 00:06:44,160 --> 00:06:49,640 Speaker 3: causes it to move? And she became deeply curious about 102 00:06:49,960 --> 00:06:54,720 Speaker 3: every little secret of nature, about the corals and about 103 00:06:54,800 --> 00:06:58,280 Speaker 3: the curves of the shells and why they're done in 104 00:06:58,320 --> 00:07:01,840 Speaker 3: a certain way. And I realized that was something other 105 00:07:01,960 --> 00:07:08,080 Speaker 3: great innovator set is this passionate curiosity about everyday things. 106 00:07:08,760 --> 00:07:11,920 Speaker 2: Walter says that around that time, Jennifer received a particular 107 00:07:11,960 --> 00:07:12,920 Speaker 2: book from her father. 108 00:07:13,560 --> 00:07:17,360 Speaker 3: Her father knew she loved to read, and used to 109 00:07:17,440 --> 00:07:21,920 Speaker 3: buy used paperbacks on the way home and leave them 110 00:07:22,000 --> 00:07:24,800 Speaker 3: on her bed for to read on Saturday. And one 111 00:07:24,840 --> 00:07:28,040 Speaker 3: day he left the paperback of the Double Helix. And 112 00:07:28,120 --> 00:07:31,040 Speaker 3: it looks like a detective book in a way. Now, 113 00:07:31,040 --> 00:07:33,559 Speaker 3: if you know the Double Helix, it's a wonderful book. 114 00:07:33,600 --> 00:07:37,880 Speaker 3: It's Jim Watson's personal account of how he and Francis 115 00:07:38,000 --> 00:07:43,080 Speaker 3: Crick and others discovered the structure of DNA, that little 116 00:07:43,120 --> 00:07:46,680 Speaker 3: double helix, and it's about their sprint to do it 117 00:07:47,080 --> 00:07:51,000 Speaker 3: and to beat other researchers to make this discovery. But 118 00:07:51,040 --> 00:07:53,680 Speaker 3: of course Jennifer didn't know that when she found the 119 00:07:53,720 --> 00:07:56,720 Speaker 3: paperback on her bed, and she said, oh, I thought 120 00:07:56,760 --> 00:07:58,880 Speaker 3: it was a detective's tale, and I saved it for 121 00:07:58,920 --> 00:08:03,640 Speaker 3: a rainy Saturday. And when I started reading, I realized, 122 00:08:03,920 --> 00:08:07,400 Speaker 3: what actually is a detective tale. It's about somebody on 123 00:08:07,600 --> 00:08:11,360 Speaker 3: the hunt to try to figure out how do genetic 124 00:08:11,800 --> 00:08:15,720 Speaker 3: information work. That seems like a pretty elevated thing, but 125 00:08:16,200 --> 00:08:18,920 Speaker 3: the way that James Watson wrote that book, it made 126 00:08:19,000 --> 00:08:20,680 Speaker 3: it feel like a detective story. 127 00:08:21,560 --> 00:08:23,600 Speaker 2: When Dalna was reading The Double Helix as a kid, 128 00:08:23,960 --> 00:08:26,880 Speaker 2: she was captivated not just by the discovery or even 129 00:08:26,880 --> 00:08:30,800 Speaker 2: the detective's tale, Isaacson says, but by one character in particular. 130 00:08:31,840 --> 00:08:35,640 Speaker 3: One of the interesting things about The Double Helix is 131 00:08:35,679 --> 00:08:39,760 Speaker 3: there's a character in it named Rosalind Franklin, very to 132 00:08:39,920 --> 00:08:43,880 Speaker 3: us in the science world, famous because she takes the 133 00:08:43,880 --> 00:08:47,920 Speaker 3: photographs that allow Watson and Crick to figure out the 134 00:08:47,960 --> 00:08:51,640 Speaker 3: double helix structure of DNA, and she doesn't get much credit. 135 00:08:51,679 --> 00:08:56,080 Speaker 3: And in the book that Watson writes, he dismisses her 136 00:08:56,160 --> 00:08:58,960 Speaker 3: a bit. He calls her Rosie, even though he takes 137 00:08:58,960 --> 00:09:03,079 Speaker 3: her science serious. And I asked Jennifer about that. When 138 00:09:03,120 --> 00:09:06,880 Speaker 3: she read the book, did she notice the dismissiveness? She said, no, 139 00:09:07,720 --> 00:09:10,520 Speaker 3: because I was so surprised that a girl could be 140 00:09:10,600 --> 00:09:14,400 Speaker 3: a scientist. And that's what I took away from the 141 00:09:14,440 --> 00:09:18,120 Speaker 3: book was I did not know women were scientists. 142 00:09:18,160 --> 00:09:21,200 Speaker 2: So she didn't find early in her life role models. 143 00:09:21,559 --> 00:09:24,800 Speaker 3: She said she had two role models. One was Rossall 144 00:09:24,840 --> 00:09:27,560 Speaker 3: and Franklin in this book, and the other she read 145 00:09:27,559 --> 00:09:32,320 Speaker 3: a childhood book about Marie Curie. And she had always 146 00:09:32,320 --> 00:09:35,120 Speaker 3: wanted to be a French teacher, and she was doing 147 00:09:35,480 --> 00:09:39,880 Speaker 3: literature even in high school. And so she told her 148 00:09:39,920 --> 00:09:43,199 Speaker 3: guidance counselor at school, I think I want to be 149 00:09:43,280 --> 00:09:47,640 Speaker 3: a scientist. And the guidance counselor in Ilo, Hawaii said, no, 150 00:09:47,840 --> 00:09:51,520 Speaker 3: girls don't do science. Well, it was a good thing 151 00:09:51,640 --> 00:09:53,800 Speaker 3: that he said that, because if you know Jennifer and 152 00:09:53,840 --> 00:09:56,600 Speaker 3: you read the book, that's going to get her back up. 153 00:09:56,800 --> 00:09:59,719 Speaker 3: And it does, and she says, then I'm going to 154 00:09:59,760 --> 00:10:04,320 Speaker 3: become a scientist. She was very lucky to have a mentor. 155 00:10:04,840 --> 00:10:07,960 Speaker 3: There was a guy named Don Hemis who taught biology 156 00:10:08,000 --> 00:10:13,280 Speaker 3: at the local college in Helo of Hawaii, and he 157 00:10:13,280 --> 00:10:15,240 Speaker 3: would go and walks on the beach with her and 158 00:10:15,400 --> 00:10:20,640 Speaker 3: collect small organisms and show the crustaceans and how they worked, 159 00:10:21,120 --> 00:10:24,640 Speaker 3: and allowed her to indulge her interests in science, and 160 00:10:24,800 --> 00:10:27,240 Speaker 3: even in the summer, would bring her into the lab 161 00:10:27,280 --> 00:10:31,000 Speaker 3: where she could look at the shells under a microscope. 162 00:10:31,240 --> 00:10:35,800 Speaker 3: And we have to realize the importance of mentorship and 163 00:10:35,920 --> 00:10:41,280 Speaker 3: also realize that sometimes science is not something that everybody 164 00:10:41,320 --> 00:10:44,080 Speaker 3: gets to be a part of. There's a lot of 165 00:10:44,200 --> 00:10:47,440 Speaker 3: underrepresented groups in science, including women. 166 00:10:47,960 --> 00:10:50,560 Speaker 2: And it seems like she once she got to college, 167 00:10:51,080 --> 00:10:53,080 Speaker 2: she did start to you know, she had a real 168 00:10:53,120 --> 00:10:55,440 Speaker 2: aptitude for science, but even then she almost was a 169 00:10:55,480 --> 00:10:59,360 Speaker 2: French wanted to become an expert in French literature instead. 170 00:11:00,120 --> 00:11:02,960 Speaker 3: Yeah, she goes to Pomona, which has a great chemistry 171 00:11:03,000 --> 00:11:06,800 Speaker 3: department and a smaller college in California. She's really out 172 00:11:06,800 --> 00:11:10,120 Speaker 3: of place because you know, she's from Hawaii and I 173 00:11:10,120 --> 00:11:14,959 Speaker 3: don't know anybody, and she's finding the chemistry hard because 174 00:11:15,000 --> 00:11:18,840 Speaker 3: she didn't know enough math. And she tells her French 175 00:11:18,920 --> 00:11:22,200 Speaker 3: teacher at college, I think I'm going to change majors 176 00:11:22,320 --> 00:11:25,679 Speaker 3: to French. I've always wanted to be a French major. 177 00:11:26,440 --> 00:11:31,640 Speaker 3: And fortunately the French professor says something. She says, you know, 178 00:11:32,000 --> 00:11:34,520 Speaker 3: if you become a French major, that's great, and you 179 00:11:34,600 --> 00:11:37,640 Speaker 3: may become a French professor. But if you become a 180 00:11:37,679 --> 00:11:40,719 Speaker 3: biology major, there's probably more open to you. 181 00:11:41,720 --> 00:11:47,200 Speaker 2: It's true, it's true. The job prospects are significantly different. 182 00:11:47,280 --> 00:11:49,720 Speaker 2: So then she ends up at Harvard, she ends up 183 00:11:49,760 --> 00:11:53,720 Speaker 2: in Jack Shostak's lab. And this seems like another sort 184 00:11:53,720 --> 00:11:57,080 Speaker 2: of pivotal moment in the sense that he conveys to 185 00:11:57,120 --> 00:12:01,199 Speaker 2: her something about doing basic science and why you're doing 186 00:12:01,240 --> 00:12:03,640 Speaker 2: it and what you're trying to capture. 187 00:12:04,160 --> 00:12:07,599 Speaker 3: Two things. He conveys the importance of basic science. In 188 00:12:07,679 --> 00:12:09,720 Speaker 3: other words, you're not supposed to be just trying to 189 00:12:09,760 --> 00:12:13,760 Speaker 3: invent a new microchip or invent a gene editing tool. 190 00:12:13,920 --> 00:12:17,520 Speaker 3: You're supposed to be marveling at the basic beauty of nature. 191 00:12:18,120 --> 00:12:22,200 Speaker 3: And secondly, he said, ask the big questions, and she said, 192 00:12:22,200 --> 00:12:25,600 Speaker 3: what's the big question? And he says, the origin of life? 193 00:12:26,080 --> 00:12:29,120 Speaker 3: How did it happen? And that's when they start looking 194 00:12:29,160 --> 00:12:32,199 Speaker 3: at RNA, a molecule that's not as famous as its 195 00:12:32,200 --> 00:12:33,080 Speaker 3: sibling DNA. 196 00:12:33,640 --> 00:12:36,040 Speaker 2: And in the book, you take us through some of 197 00:12:36,080 --> 00:12:38,719 Speaker 2: the history of how these discoveries were made, and we 198 00:12:38,760 --> 00:12:41,040 Speaker 2: don't have to go through the whole history of it. 199 00:12:41,080 --> 00:12:44,199 Speaker 2: But you know, Darwin to Gregor Mendel oh, let's we 200 00:12:44,960 --> 00:12:45,880 Speaker 2: certainly can. 201 00:12:46,120 --> 00:12:49,760 Speaker 3: Well, you gotta start with Darwin and Mendel, both in 202 00:12:49,800 --> 00:12:53,400 Speaker 3: the same periods on the mid eighteen hundreds. And what 203 00:12:53,720 --> 00:12:57,400 Speaker 3: Darwin figures out by going on the voyage of the beagles, 204 00:12:57,400 --> 00:13:02,360 Speaker 3: of the galopgos and others is different species adapt as 205 00:13:02,400 --> 00:13:05,440 Speaker 3: their environment changes. He looks at the beaks of the 206 00:13:05,480 --> 00:13:08,200 Speaker 3: finches and like, oh, maybe they had a drought and 207 00:13:08,240 --> 00:13:11,240 Speaker 3: a beak become something that can open up nuts. So 208 00:13:11,280 --> 00:13:15,200 Speaker 3: he's trying to figure out how does this information, this 209 00:13:15,600 --> 00:13:21,400 Speaker 3: survival of the fittest lead to changes in the genetic information. 210 00:13:22,040 --> 00:13:25,560 Speaker 3: And at the same time, unbeknownst to him, there's a 211 00:13:25,600 --> 00:13:30,160 Speaker 3: priest in Burno, which is the Czech Republic now, who 212 00:13:30,240 --> 00:13:33,719 Speaker 3: is breeding peas, and he would say, okay, I like 213 00:13:33,800 --> 00:13:36,640 Speaker 3: the peas with the purple coat, and when I mix 214 00:13:36,720 --> 00:13:39,160 Speaker 3: them with the peas with the white coat, they don't 215 00:13:39,200 --> 00:13:43,559 Speaker 3: sort of blend purple and white. They'll have a dominant 216 00:13:43,600 --> 00:13:46,840 Speaker 3: gene so most turnout purple, but one will turn out 217 00:13:46,880 --> 00:13:50,400 Speaker 3: white in the second generation. So all of that information 218 00:13:50,480 --> 00:13:55,200 Speaker 3: comes together and they finally discover around nineteen hundred there 219 00:13:55,360 --> 00:14:01,079 Speaker 3: just must be some chemical in our body that transmits 220 00:14:01,440 --> 00:14:06,160 Speaker 3: this genetic information, and that's where the hunt begins for 221 00:14:06,320 --> 00:14:09,000 Speaker 3: how does genetic information get transmitted. 222 00:14:10,160 --> 00:14:12,559 Speaker 2: Coming up after the break we dive into the Human 223 00:14:12,600 --> 00:14:17,240 Speaker 2: Genome project and why some scientists, notably women, didn't get 224 00:14:17,240 --> 00:14:18,160 Speaker 2: the chance to work on it. 225 00:14:30,240 --> 00:14:34,040 Speaker 3: The big breakthrough around nineteen fifty or so is when 226 00:14:34,120 --> 00:14:39,479 Speaker 3: James Watson and Francis Kraik get together in Cambridge University, 227 00:14:39,560 --> 00:14:44,480 Speaker 3: England and they figure out the DNS structure, which is 228 00:14:44,520 --> 00:14:49,320 Speaker 3: it has two strands and it's like a spiral staircase, 229 00:14:49,720 --> 00:14:53,640 Speaker 3: and the rungs are four different letters. We'll call out 230 00:14:53,720 --> 00:14:59,680 Speaker 3: for chemicals ATCG and it can pull itself. It pulls 231 00:14:59,760 --> 00:15:04,960 Speaker 3: upon and replicates itself, and those letters three billion pairs 232 00:15:04,960 --> 00:15:09,080 Speaker 3: of code to code you and me that encodes the 233 00:15:09,160 --> 00:15:13,080 Speaker 3: genetic information that gets transferred generation to generation. 234 00:15:13,760 --> 00:15:16,600 Speaker 2: This string of findings from Darwin to Watson and Crick 235 00:15:17,080 --> 00:15:19,800 Speaker 2: with a foundation for the study of DNA. But fast 236 00:15:19,840 --> 00:15:22,520 Speaker 2: forward two decades later and Jennifer DOWDNA and our mentor 237 00:15:22,560 --> 00:15:26,240 Speaker 2: at Harvard doctor Jack Showsteck. We're paying attention to another 238 00:15:26,240 --> 00:15:29,560 Speaker 2: important but more neglected molecule, RNA. 239 00:15:30,520 --> 00:15:34,520 Speaker 3: The different molecules we have in our body, proteins being 240 00:15:34,680 --> 00:15:38,320 Speaker 3: among the most famous, but there's also what they're called 241 00:15:38,400 --> 00:15:43,760 Speaker 3: nucleic acids, and they're two of them, RNA and DNA. 242 00:15:44,320 --> 00:15:50,080 Speaker 3: And DNA is what encodes our heredity, our genes. They 243 00:15:50,120 --> 00:15:54,320 Speaker 3: are encoded in this four letter code that can replicate 244 00:15:54,360 --> 00:15:57,280 Speaker 3: itself because the strands of DNA can pull apart and 245 00:15:57,320 --> 00:16:02,120 Speaker 3: then create an identical new set of DNA strands. That's 246 00:16:02,200 --> 00:16:07,160 Speaker 3: how we transmit genetic information. But the real question is 247 00:16:08,480 --> 00:16:12,320 Speaker 3: what makes that work, and that's what RNA does. It's 248 00:16:12,320 --> 00:16:15,680 Speaker 3: not as famous, but like a lot of not famous siblings, 249 00:16:15,680 --> 00:16:19,080 Speaker 3: it actually does more work because the DNA just sits 250 00:16:19,120 --> 00:16:22,920 Speaker 3: there in the nucleus of your cell, curating this information. 251 00:16:23,080 --> 00:16:27,440 Speaker 3: It can't go anywhere. He carefully guards it. But RNA 252 00:16:27,680 --> 00:16:32,760 Speaker 3: goes into the nucleus, reads that blueprint, reads that information 253 00:16:32,960 --> 00:16:35,960 Speaker 3: in the DNA code, and then goes to the outer 254 00:16:37,000 --> 00:16:41,120 Speaker 3: area of the cell where proteins are made, and it 255 00:16:41,160 --> 00:16:44,920 Speaker 3: will make a protein based on the information it got 256 00:16:45,000 --> 00:16:50,160 Speaker 3: from DNA. And that's all life is is proteins getting made. 257 00:16:50,600 --> 00:16:53,440 Speaker 3: Whether it's your fingernails, your hair, or the neurons in 258 00:16:53,480 --> 00:16:57,000 Speaker 3: your brain or the muscles that twitch, those are just 259 00:16:57,080 --> 00:17:02,520 Speaker 3: different forms of protein that use the code in our genes, 260 00:17:03,080 --> 00:17:05,919 Speaker 3: and it's RNA that said, all right, we're now going 261 00:17:05,960 --> 00:17:09,399 Speaker 3: to build a molecule that's a hair follicle. 262 00:17:10,520 --> 00:17:13,680 Speaker 2: In that lab, Dauna and her colleagues were focused squarely 263 00:17:13,720 --> 00:17:15,280 Speaker 2: on RNA. 264 00:17:15,680 --> 00:17:19,160 Speaker 3: DNA knows how to replicate itself, that's its strong sort. 265 00:17:19,280 --> 00:17:23,840 Speaker 3: That's why it's DNA. Rna they figured out could also 266 00:17:24,200 --> 00:17:30,080 Speaker 3: replicate itself and help create proteins, and so it could 267 00:17:30,119 --> 00:17:35,639 Speaker 3: have been the original molecule that gets life started. And 268 00:17:35,760 --> 00:17:40,679 Speaker 3: indeed they do a paper about self replicating RNA and 269 00:17:40,800 --> 00:17:44,040 Speaker 3: set the groundwork for which it's now called the RNA world, 270 00:17:44,520 --> 00:17:47,359 Speaker 3: which is how did life begin? Well, there was this 271 00:17:47,600 --> 00:17:50,000 Speaker 3: stew of a lot of chemicals and four of them 272 00:17:50,040 --> 00:17:54,919 Speaker 3: get together and they start replicating. And it made her 273 00:17:55,080 --> 00:17:58,600 Speaker 3: always want to look at basic science and the big 274 00:17:58,680 --> 00:17:59,679 Speaker 3: questions of life. 275 00:18:00,160 --> 00:18:02,760 Speaker 2: Is that the paper that landed her at Cold Spring 276 00:18:03,119 --> 00:18:05,600 Speaker 2: giving the talk at age twenty. 277 00:18:05,320 --> 00:18:10,639 Speaker 3: Three, absolutely the research with Jack shaw Stack into the 278 00:18:10,800 --> 00:18:15,119 Speaker 3: RNA world and how you could have RNA replicate itself 279 00:18:15,200 --> 00:18:19,520 Speaker 3: and do all these amazing things. That she gets invited 280 00:18:19,560 --> 00:18:22,560 Speaker 3: by the great James Watson, whose Double Helix she had 281 00:18:22,600 --> 00:18:25,600 Speaker 3: read as a kid, to come to cold Spring Harbor 282 00:18:25,720 --> 00:18:30,280 Speaker 3: lab on Long Island where they have scientific conferences because 283 00:18:30,359 --> 00:18:33,719 Speaker 3: Jack shaw Stack couldn't come, and so she gets to 284 00:18:33,840 --> 00:18:39,240 Speaker 3: present their work with James Watson sitting in the front row, 285 00:18:39,680 --> 00:18:41,720 Speaker 3: and this is a seminal experience for her. 286 00:18:42,280 --> 00:18:45,280 Speaker 2: Isaacson tells me that for DOWDNA, the Cold Spring Harbor 287 00:18:45,320 --> 00:18:48,240 Speaker 2: conference was not just a full circle moment, but a 288 00:18:48,280 --> 00:18:51,480 Speaker 2: signal that she was joining this historical chain of discovery, 289 00:18:52,119 --> 00:18:56,240 Speaker 2: a generational project aimed at ultimately unraveling how our genes work. 290 00:18:57,000 --> 00:18:59,440 Speaker 2: But down it wasn't alone. There was an expanding group 291 00:18:59,440 --> 00:19:02,480 Speaker 2: of researchers who were turning their attention to RNA. It 292 00:19:02,520 --> 00:19:05,280 Speaker 2: feels like when DAWDNA is sort of starting to come 293 00:19:05,280 --> 00:19:08,680 Speaker 2: of age as a scientist's you know, she's working in 294 00:19:08,680 --> 00:19:11,640 Speaker 2: different labs. There's this next big development going on, which 295 00:19:11,680 --> 00:19:13,720 Speaker 2: is the Human Genome Project, and that's sort of what's 296 00:19:13,760 --> 00:19:17,639 Speaker 2: hovering over everything. But she goes in a different direction, 297 00:19:17,680 --> 00:19:20,520 Speaker 2: and maybe you can explain what the Human Genome Project 298 00:19:20,560 --> 00:19:24,600 Speaker 2: was doing and why she kind of went the other way. 299 00:19:24,960 --> 00:19:28,600 Speaker 3: So in the nineteen fifties, when Watching and Krick discover 300 00:19:28,880 --> 00:19:33,439 Speaker 3: the structure of DNA, the hunt becomes let's look at 301 00:19:33,520 --> 00:19:37,800 Speaker 3: each of those letters and decode where in our DNA 302 00:19:38,040 --> 00:19:42,000 Speaker 3: it codes for hair height, whatever may be encoded for. 303 00:19:42,400 --> 00:19:45,960 Speaker 3: And that was called the Human Genome Project, which is 304 00:19:46,200 --> 00:19:50,080 Speaker 3: map the human gene and one of the leaders was 305 00:19:50,200 --> 00:19:54,399 Speaker 3: James Watson, and Francis Crick was very involved too. It 306 00:19:54,600 --> 00:19:58,680 Speaker 3: culminated in the year two thousand, more. 307 00:19:58,520 --> 00:20:02,080 Speaker 5: Than a thousand of searches across six nations have revealed 308 00:20:02,080 --> 00:20:06,320 Speaker 5: nearly all three billion letters of our miraculous genetic code. 309 00:20:06,480 --> 00:20:10,159 Speaker 5: I congratulate all of you on the stunning and humbling achievement. 310 00:20:11,520 --> 00:20:14,919 Speaker 3: I was at Time magazine and we put Francis Collins 311 00:20:15,600 --> 00:20:19,480 Speaker 3: and Craig Ventnor on the cover. They were rivals trying 312 00:20:19,520 --> 00:20:22,679 Speaker 3: to decode the gene. We were going to just do 313 00:20:22,760 --> 00:20:25,320 Speaker 3: Craig Venter. And the little thing was that the vice 314 00:20:25,359 --> 00:20:28,359 Speaker 3: president was Al Gore, and he was insistent. He even 315 00:20:28,480 --> 00:20:31,600 Speaker 3: called and said, you also have to put the National 316 00:20:31,600 --> 00:20:35,280 Speaker 3: Institutes of Health person, the government person. Yeah, he called 317 00:20:35,359 --> 00:20:39,879 Speaker 3: and said, you can't just put this privateer who's doing it. 318 00:20:40,400 --> 00:20:42,679 Speaker 3: And so we put them both on the cover and 319 00:20:42,720 --> 00:20:44,320 Speaker 3: we thought it was the biggest thing in the world 320 00:20:44,359 --> 00:20:47,720 Speaker 3: that all of human life would now change, because we 321 00:20:47,800 --> 00:20:52,879 Speaker 3: could read the blueprint of the discovery of our human genome. 322 00:20:53,200 --> 00:20:55,840 Speaker 3: It was a big deal back then. Then Dolly the 323 00:20:55,920 --> 00:21:00,280 Speaker 3: Sheep was being cloned, and everybody thought that DNA was 324 00:21:00,359 --> 00:21:04,600 Speaker 3: going to be a revolution, And like a lot of revolutions, 325 00:21:05,160 --> 00:21:10,000 Speaker 3: it actually started slowly. Why because we could now read 326 00:21:10,640 --> 00:21:13,520 Speaker 3: the code of life, but we couldn't do anything with it. 327 00:21:13,680 --> 00:21:16,040 Speaker 3: You couldn't rewrite it, you couldn't edit it. 328 00:21:16,640 --> 00:21:19,879 Speaker 2: But there was this sense then that well, now we 329 00:21:19,960 --> 00:21:21,240 Speaker 2: have command of this thing. 330 00:21:21,280 --> 00:21:21,639 Speaker 3: We know. 331 00:21:22,240 --> 00:21:24,040 Speaker 2: Now, we'll just figure out what all the genes do, 332 00:21:24,720 --> 00:21:27,320 Speaker 2: and then we'll be able to manipulate them. Down the line, 333 00:21:27,359 --> 00:21:30,480 Speaker 2: we'll be able to cure diseases. But everyone was forgetting 334 00:21:30,520 --> 00:21:33,159 Speaker 2: about another element, which was RNA. 335 00:21:34,119 --> 00:21:36,719 Speaker 3: It was quite nice to be able to say, oh, 336 00:21:36,760 --> 00:21:39,560 Speaker 3: that's the part of the gene that does this, but 337 00:21:39,680 --> 00:21:42,480 Speaker 3: let's say it's the letter in the gene that's messed 338 00:21:42,560 --> 00:21:47,560 Speaker 3: up that causes sickle cell anemia. That was fine to know, 339 00:21:47,920 --> 00:21:51,960 Speaker 3: but there wasn't much useful that came out of it, 340 00:21:52,400 --> 00:21:56,280 Speaker 3: And that's when RNA and the women who were focusing 341 00:21:56,320 --> 00:21:59,560 Speaker 3: on RNA entered the story. One of the things that 342 00:21:59,640 --> 00:22:03,480 Speaker 3: happened is the Human Genome Project and decoding DNA is 343 00:22:03,840 --> 00:22:08,720 Speaker 3: mainly an alpha male exercise. Jennifer Dowden, when she played 344 00:22:08,880 --> 00:22:11,520 Speaker 3: soccer as a little kid in Hawaii, she said, all 345 00:22:11,560 --> 00:22:13,960 Speaker 3: the boys used to run to the ball, but I 346 00:22:14,000 --> 00:22:16,920 Speaker 3: always wanted to run to where the ball was going 347 00:22:16,960 --> 00:22:19,520 Speaker 3: to be. And so a lot of women who were 348 00:22:19,520 --> 00:22:24,240 Speaker 3: not part of the Human Genome Project started studying RNA, 349 00:22:24,680 --> 00:22:29,800 Speaker 3: the less famous molecule, and those were people like Jillian Vanfield, 350 00:22:30,119 --> 00:22:36,199 Speaker 3: Emmanuel Scharpanche, Kati Carichko, and of course Jennifer DOWDNA. In 351 00:22:36,280 --> 00:22:38,880 Speaker 3: the end, it turns out that RNA is a lot 352 00:22:39,000 --> 00:22:42,920 Speaker 3: more useful to understand because it's the one that goes 353 00:22:42,960 --> 00:22:46,479 Speaker 3: and does work, reads the DNA, and then has the 354 00:22:46,520 --> 00:22:49,639 Speaker 3: protein made. It also can be a messenger to make 355 00:22:49,680 --> 00:22:52,600 Speaker 3: any protein you want, which is quite useful when you're 356 00:22:52,600 --> 00:22:55,399 Speaker 3: trying to invent a COVID vaccine and you want to 357 00:22:55,400 --> 00:23:00,560 Speaker 3: make a fake spike protein in people's cells. So a 358 00:23:00,680 --> 00:23:05,480 Speaker 3: lot of women were doing RNA, and after the Human 359 00:23:05,520 --> 00:23:09,600 Speaker 3: Genome Project, it became important to say, well, what are 360 00:23:09,600 --> 00:23:11,919 Speaker 3: we going to do with all this information. We have 361 00:23:11,960 --> 00:23:13,879 Speaker 3: to be able to manipulate it, we have to edit it, 362 00:23:13,880 --> 00:23:16,560 Speaker 3: we have to do things with it. And that's where 363 00:23:16,760 --> 00:23:20,240 Speaker 3: RNA becomes the tool just like in our body. It's 364 00:23:20,280 --> 00:23:24,960 Speaker 3: a tool for applying the code of DNA to the 365 00:23:25,000 --> 00:23:30,040 Speaker 3: making of protein. In science and the basic research, it 366 00:23:30,119 --> 00:23:34,080 Speaker 3: becomes the tool for understanding what we can do with 367 00:23:34,160 --> 00:23:35,240 Speaker 3: our genetic coding. 368 00:23:35,640 --> 00:23:38,119 Speaker 2: Isaacson says that in order to really understand how to 369 00:23:38,160 --> 00:23:41,480 Speaker 2: harness the abilities of RNA, Jennifer Downer realized that she 370 00:23:41,560 --> 00:23:43,639 Speaker 2: had to use some of the same techniques deployed by 371 00:23:43,720 --> 00:23:48,000 Speaker 2: Roslin Franklin to uncover the structure of DNA, namely an 372 00:23:48,080 --> 00:23:52,959 Speaker 2: imaging technology called X ray crystallography, which, as Isaacson writes, 373 00:23:53,200 --> 00:23:55,760 Speaker 2: she could use to figure out the folds and twists 374 00:23:55,920 --> 00:23:58,880 Speaker 2: of the three dimensional structure of self splicing RNA. 375 00:23:59,119 --> 00:24:03,640 Speaker 3: She had understand stood from Jack show Stack the important 376 00:24:03,680 --> 00:24:08,359 Speaker 3: of RNA in how RNA explained the origins of life. 377 00:24:08,440 --> 00:24:12,520 Speaker 3: So she's doing things about the structure of RNA, trying 378 00:24:12,560 --> 00:24:15,600 Speaker 3: to crystallize that. That's the way scientists are able to 379 00:24:15,640 --> 00:24:18,359 Speaker 3: figure out what does it really look like? You know, 380 00:24:18,440 --> 00:24:20,439 Speaker 3: how can I shine light into it? It is what 381 00:24:20,600 --> 00:24:24,200 Speaker 3: Rosalind Franklin did for DNA, so that we can see 382 00:24:24,240 --> 00:24:26,240 Speaker 3: the structure in the shape mm hmm. 383 00:24:26,680 --> 00:24:29,760 Speaker 2: And it seems like Jennifer downas she really she had 384 00:24:29,800 --> 00:24:32,719 Speaker 2: that maybe that soccer player moving to where the ball 385 00:24:32,840 --> 00:24:36,400 Speaker 2: is going to be sense of there's something here that 386 00:24:36,720 --> 00:24:39,760 Speaker 2: we're going to need to know, and there's basic science 387 00:24:39,760 --> 00:24:41,800 Speaker 2: to be done here. And I feel like her first 388 00:24:42,200 --> 00:24:44,800 Speaker 2: the first time she sort of has a public profile, 389 00:24:45,320 --> 00:24:47,480 Speaker 2: is like a little story that you found when she's 390 00:24:47,480 --> 00:24:50,760 Speaker 2: at Yale. She's working on the structure of RNA and 391 00:24:51,720 --> 00:24:54,120 Speaker 2: there's a very moving scene where she's trying to resolve 392 00:24:54,160 --> 00:24:58,360 Speaker 2: this question and her father is dying at the same time, her. 393 00:24:58,200 --> 00:25:01,280 Speaker 3: Father was dying, and her father it was this great influence. 394 00:25:01,320 --> 00:25:04,240 Speaker 3: It always pushed her to be a scientist, and he 395 00:25:04,359 --> 00:25:07,440 Speaker 3: kept saying, even though he was fighting cancer, kept saying, 396 00:25:07,480 --> 00:25:10,679 Speaker 3: explain it to me, Explain what you're doing. And that 397 00:25:10,800 --> 00:25:15,439 Speaker 3: becomes one of Jennifer Dowden's superpowers is being able to 398 00:25:15,560 --> 00:25:18,000 Speaker 3: explain what was happening. 399 00:25:19,440 --> 00:25:21,919 Speaker 2: What she explained to her father was her first taste 400 00:25:21,920 --> 00:25:25,600 Speaker 2: of real scientific discovery, a picture of the three dimensional 401 00:25:25,600 --> 00:25:29,240 Speaker 2: folded shape of an RNA molecule. But for DOWDNA and 402 00:25:29,240 --> 00:25:32,560 Speaker 2: her expanding orbit of colleagues, kneeling the structure of RNA 403 00:25:32,680 --> 00:25:35,439 Speaker 2: was just the beginning to figure out how to harness 404 00:25:35,440 --> 00:25:38,040 Speaker 2: that structure. She would need to piggyback on an obscure 405 00:25:38,119 --> 00:25:40,879 Speaker 2: breakthrough from across the ocean in Spain. 406 00:25:42,680 --> 00:25:48,080 Speaker 3: A graduate student, young scientist in Spain, and he's looking 407 00:25:48,160 --> 00:25:54,920 Speaker 3: at bacteria in very, very salty ponds and he notices 408 00:25:55,000 --> 00:25:59,000 Speaker 3: something when he's sequencing the genes, and he keeps seeing 409 00:25:59,480 --> 00:26:05,439 Speaker 3: these pedit sequences, but nobody knows why they exist, and 410 00:26:05,520 --> 00:26:07,120 Speaker 3: that's when the hunt begins. 411 00:26:08,000 --> 00:26:10,520 Speaker 2: Coming out this season on chrispur. 412 00:26:10,520 --> 00:26:15,240 Speaker 3: There's a race around the world. It's dangerous because scientists 413 00:26:15,280 --> 00:26:19,200 Speaker 3: are sometimes competitive. They want to get their paper published first. 414 00:26:19,680 --> 00:26:21,720 Speaker 3: They want to win the prize, they want to get 415 00:26:21,720 --> 00:26:25,320 Speaker 3: the patent. Not only will we be able to cut, 416 00:26:25,440 --> 00:26:28,640 Speaker 3: DNA will cut and paste just as if we were 417 00:26:28,720 --> 00:26:34,040 Speaker 3: using a word processor. Jennifer had a nightmare and it 418 00:26:34,240 --> 00:26:38,040 Speaker 3: was that somebody wanted to meet with her about this 419 00:26:38,119 --> 00:26:41,359 Speaker 3: new technology. And she opens the door to the room. 420 00:26:41,560 --> 00:26:46,359 Speaker 3: The person looks up and it's Adolph Hitler, and she's 421 00:26:46,440 --> 00:26:51,320 Speaker 3: taken aback and she realizes, of course, that in the 422 00:26:51,359 --> 00:26:58,240 Speaker 3: wrong hands, this tool could be not just powerful, but evil. 423 00:27:00,359 --> 00:27:02,760 Speaker 2: On Crisper, the Story of Jennifer DOWDNA is a production 424 00:27:02,800 --> 00:27:05,600 Speaker 2: of Kaleidoscope and iHeart. This show is based on the 425 00:27:05,600 --> 00:27:08,480 Speaker 2: writing and reporting of Walter Isaacson. It's hosted by me 426 00:27:08,520 --> 00:27:11,400 Speaker 2: Evan Ratliffe and produced by Adrianna Tapia with assistance from 427 00:27:11,440 --> 00:27:14,439 Speaker 2: Alex Zonoveld. It was mixed by Kyle Murdoch and our 428 00:27:14,480 --> 00:27:17,800 Speaker 2: studio engineer was Thomas Walsh. Our executive producers are Kate 429 00:27:17,840 --> 00:27:22,240 Speaker 2: Osbourne and Mangashatigador from Kaleidoscope and Katrina Norvell from iHeart Podcasts. 430 00:27:22,520 --> 00:27:25,399 Speaker 2: If you enjoy hearing stories about visionaries and science technology, 431 00:27:25,680 --> 00:27:27,840 Speaker 2: check out our other seasons based on the biographies that 432 00:27:27,880 --> 00:27:31,280 Speaker 2: Walter Aakson's written. On Musk for an intimate dive into 433 00:27:31,320 --> 00:27:34,400 Speaker 2: all the facets of Elon Musk and on Benjamin Franklin 434 00:27:34,560 --> 00:27:37,879 Speaker 2: to understand how his scientific curiosity shapes society as we 435 00:27:38,000 --> 00:27:39,439 Speaker 2: know it. Thanks for listening.