1 00:00:11,520 --> 00:00:14,120 Speaker 1: Last year in Philadelphia, the mother and father of a 2 00:00:14,160 --> 00:00:18,119 Speaker 1: baby boy experienced any newborn parents' nightmare. They discovered that 3 00:00:18,120 --> 00:00:21,079 Speaker 1: their son, kJ had been born with a rare genetic 4 00:00:21,079 --> 00:00:24,880 Speaker 1: disease called urea cycle disorder, causing him to have abnormally 5 00:00:24,960 --> 00:00:29,000 Speaker 1: high levels of ammonia in his blood. The prognosis was devastating, 6 00:00:29,400 --> 00:00:32,320 Speaker 1: and the only conventional life saving treatment option was a 7 00:00:32,320 --> 00:00:35,400 Speaker 1: liver transplant, a treatment that kJ might not be able 8 00:00:35,400 --> 00:00:40,360 Speaker 1: to obtain or survive. But then a pair of doctors 9 00:00:40,360 --> 00:00:44,000 Speaker 1: at the Children's Hospital in Philadelphia approached Kj's family to 10 00:00:44,000 --> 00:00:46,560 Speaker 1: discuss the possibility of trying a treatment that had never 11 00:00:46,600 --> 00:00:49,560 Speaker 1: been tried before. They would try using a technology called 12 00:00:49,640 --> 00:00:53,440 Speaker 1: Crisper to correct the specific genetic flaws that were creating 13 00:00:53,479 --> 00:00:54,320 Speaker 1: Kj's condition. 14 00:00:55,480 --> 00:00:59,280 Speaker 2: So it takes about six months, and the doctors developed 15 00:00:59,280 --> 00:01:05,399 Speaker 2: a drug that was designed to target Babykj's genetic variant, 16 00:01:05,880 --> 00:01:11,240 Speaker 2: specifically targeted to that one letter mess up in his DNA. 17 00:01:12,080 --> 00:01:15,040 Speaker 2: In just a few days after his first injection, kJ 18 00:01:15,240 --> 00:01:19,199 Speaker 2: starts showing signs of improvement. It's totally miraculous. The color 19 00:01:19,240 --> 00:01:22,080 Speaker 2: returns to his cheeks and for the first time, he 20 00:01:22,120 --> 00:01:26,800 Speaker 2: can tolerate protein in his diet. His parents are overwhelmed. 21 00:01:27,319 --> 00:01:30,800 Speaker 2: After two months, the doctors described him as growing and 22 00:01:30,920 --> 00:01:34,160 Speaker 2: thriving with no side effects from the treatment, And with 23 00:01:34,280 --> 00:01:38,280 Speaker 2: every month the hope has grown that the world's first 24 00:01:38,840 --> 00:01:46,479 Speaker 2: personalized gene editing treatment has been a complete success. Now 25 00:01:46,480 --> 00:01:50,440 Speaker 2: you may think that therapy was developed over six months, 26 00:01:50,680 --> 00:01:53,720 Speaker 2: but it was actually the product of like thirty years 27 00:01:53,840 --> 00:01:56,840 Speaker 2: of biological research. I mean, there was a lot of 28 00:01:56,920 --> 00:02:01,120 Speaker 2: technological development that went into this race. To arrive at 29 00:02:01,120 --> 00:02:04,320 Speaker 2: this moment is just a great story of ambition and 30 00:02:04,360 --> 00:02:09,440 Speaker 2: competition and collaboration and triumph because the work and the 31 00:02:09,480 --> 00:02:14,120 Speaker 2: results are extraordinary, and much of it was fueled by 32 00:02:14,120 --> 00:02:19,680 Speaker 2: the quiet determination of a biochemist named Jennifer Dowdner. And 33 00:02:19,720 --> 00:02:21,320 Speaker 2: while that name may not be at the tip of 34 00:02:21,360 --> 00:02:23,720 Speaker 2: your tongue like Elon Musk or Steve Jobs or maybe 35 00:02:23,760 --> 00:02:27,440 Speaker 2: Benjamin Franklin, who work might be the thing that saves 36 00:02:27,560 --> 00:02:31,640 Speaker 2: your family like a different kJ or maybe it already did, 37 00:02:32,080 --> 00:02:35,600 Speaker 2: like with the COVID vaccine. 38 00:02:42,520 --> 00:02:45,600 Speaker 3: You know, we've never had in the past the ability 39 00:02:45,720 --> 00:02:50,359 Speaker 3: to change the fundamental chemical nature of who we are 40 00:02:50,880 --> 00:02:53,800 Speaker 3: in this way, right, and now we do and what 41 00:02:53,840 --> 00:02:54,359 Speaker 3: do we do with that? 42 00:02:57,760 --> 00:03:01,720 Speaker 2: The discovery is both a tale of ure, curiosity driven 43 00:03:01,800 --> 00:03:05,800 Speaker 2: basic science as well as functional science. 44 00:03:07,320 --> 00:03:09,360 Speaker 1: This is the third time I've sat down with Isaacson 45 00:03:09,639 --> 00:03:12,600 Speaker 1: as part of an ongoing conversation we're having about his subjects, 46 00:03:12,960 --> 00:03:14,600 Speaker 1: the kind of people who changed the world by the 47 00:03:14,600 --> 00:03:17,440 Speaker 1: force of their intellect. In the first season, we talked 48 00:03:17,440 --> 00:03:21,240 Speaker 1: about Elon Musk and Isaacson's six hundred page biography of him, 49 00:03:21,560 --> 00:03:24,320 Speaker 1: the tone that launched a thousand hot takes. In our 50 00:03:24,320 --> 00:03:28,160 Speaker 1: second we focused on a less polarizing inventor, Benjamin Franklin, 51 00:03:28,320 --> 00:03:30,440 Speaker 1: whose life in thinking helped us make sense of today's 52 00:03:30,440 --> 00:03:34,000 Speaker 1: turbulent times. The origins of our third sit down traced 53 00:03:34,000 --> 00:03:36,840 Speaker 1: back to twenty twelve, when the world first heard about 54 00:03:36,840 --> 00:03:39,960 Speaker 1: a new gene editing tool called Crisper, a breakthrough that 55 00:03:40,000 --> 00:03:42,960 Speaker 1: would allow us to modify our own genes, copying and 56 00:03:42,960 --> 00:03:47,000 Speaker 1: pasting them like a sentence. Isaacson, when he learned the news, 57 00:03:47,240 --> 00:03:50,520 Speaker 1: saw it as something more than a singular invention. To him, 58 00:03:50,520 --> 00:03:53,720 Speaker 1: it represented, as he's written, the beginning of the third 59 00:03:53,720 --> 00:03:57,000 Speaker 1: great Revolution of modern times, followed by the revolutions in 60 00:03:57,000 --> 00:03:59,000 Speaker 1: physics and information technology. 61 00:04:00,080 --> 00:04:03,440 Speaker 2: Trying to create a pantheon of books about great geniuses 62 00:04:03,520 --> 00:04:07,800 Speaker 2: and the scientific revolutions. They were creating Einstein, who brings 63 00:04:07,840 --> 00:04:11,040 Speaker 2: us into the atomic era, Steve Jobs, who brought us 64 00:04:11,040 --> 00:04:15,720 Speaker 2: into the digital age. But also we're entering an age 65 00:04:15,960 --> 00:04:20,320 Speaker 2: of a life sciences revolution, and I wanted to find 66 00:04:20,440 --> 00:04:27,159 Speaker 2: somebody who represented this revolution. He was this brilliant, understated person, 67 00:04:27,320 --> 00:04:31,880 Speaker 2: this woman who wasn't mercurial or cantankerous like Steve Jobs 68 00:04:31,960 --> 00:04:35,919 Speaker 2: or Elon Musk, but was quietly leading a revolution. She 69 00:04:36,040 --> 00:04:39,120 Speaker 2: wasn't just cloning sheep. She was pushing through technologies at 70 00:04:39,120 --> 00:04:43,560 Speaker 2: are life changing. And I thought, hey, I need to 71 00:04:43,600 --> 00:04:44,640 Speaker 2: spend time with her. 72 00:04:47,440 --> 00:04:50,960 Speaker 1: I'm Evan rightlift. And this is on Crisper, The Story 73 00:04:51,000 --> 00:05:04,120 Speaker 1: of Jennifer DOWDNAT Episode one. Beginnings for Isacson. The tale 74 00:05:04,120 --> 00:05:06,840 Speaker 1: of how Jennifer down a delivered Crisper has its deepest 75 00:05:06,880 --> 00:05:09,359 Speaker 1: roots in her childhood in Hilo, Hawaii. 76 00:05:11,160 --> 00:05:14,640 Speaker 2: She's in Hawaii and she's looking at things like sleeping grass, 77 00:05:15,320 --> 00:05:19,120 Speaker 2: where if you touch it it curls up. I remember that. 78 00:05:19,200 --> 00:05:22,440 Speaker 2: I remember touching farnes. They curl up, But I didn't 79 00:05:22,480 --> 00:05:26,120 Speaker 2: sit there and obsess like, how does the leaf know 80 00:05:26,200 --> 00:05:29,000 Speaker 2: how to do? It? Does have a motor inside? 81 00:05:29,480 --> 00:05:30,520 Speaker 1: What causes it? 82 00:05:30,560 --> 00:05:36,360 Speaker 2: To move, and she became deeply curious about every little 83 00:05:36,400 --> 00:05:41,800 Speaker 2: secret of nature, about the corals, and about the curves 84 00:05:41,839 --> 00:05:44,840 Speaker 2: of the shells and why they're done in a certain way. 85 00:05:45,600 --> 00:05:49,320 Speaker 2: And I realized that was something other great innovators hat 86 00:05:49,520 --> 00:05:53,520 Speaker 2: is this passionate curiosity about everyday things. 87 00:05:54,480 --> 00:05:57,640 Speaker 1: Walter says that around that time, Jennifer received a particular 88 00:05:57,680 --> 00:05:58,640 Speaker 1: book from her father. 89 00:05:59,279 --> 00:06:03,120 Speaker 2: Her father knew she loved to read, and used to 90 00:06:03,160 --> 00:06:07,640 Speaker 2: buy used paperbacks on the way home and leave them 91 00:06:07,680 --> 00:06:10,480 Speaker 2: on her bed for to read on Saturday. And one 92 00:06:10,560 --> 00:06:13,760 Speaker 2: day he left the paperback of the Double Helix. And 93 00:06:13,839 --> 00:06:16,719 Speaker 2: it looks like a detective book in a way. Now, 94 00:06:16,760 --> 00:06:19,279 Speaker 2: if you know the Double Helix, it's a wonderful book. 95 00:06:19,320 --> 00:06:23,640 Speaker 2: It's Jim Watson's personal account of how he and Francis 96 00:06:23,720 --> 00:06:28,799 Speaker 2: Crick and others discovered the structure of DNA, that little 97 00:06:28,800 --> 00:06:32,400 Speaker 2: double helix, and it's about their sprint to do it 98 00:06:32,800 --> 00:06:36,680 Speaker 2: and to beat other researchers to make this discovery. But 99 00:06:36,760 --> 00:06:39,400 Speaker 2: of course Jennifer didn't know that when she found the 100 00:06:39,440 --> 00:06:42,440 Speaker 2: paperback on her bed, and she said, oh, I thought 101 00:06:42,440 --> 00:06:44,599 Speaker 2: it was a detective's tale. And I saved it for 102 00:06:44,640 --> 00:06:49,400 Speaker 2: a rainy Saturday and when I started reading, I realized, 103 00:06:49,640 --> 00:06:53,120 Speaker 2: what actually is a detective tale. It's about somebody on 104 00:06:53,320 --> 00:06:57,080 Speaker 2: the hunt to try to figure out how to genetic 105 00:06:57,520 --> 00:07:01,440 Speaker 2: information work. That seems like a pretty elevated thing, but 106 00:07:01,920 --> 00:07:04,640 Speaker 2: the way that James Watson wrote that book, it made 107 00:07:04,680 --> 00:07:06,400 Speaker 2: it feel like a detective story. 108 00:07:07,279 --> 00:07:09,280 Speaker 1: When Daltna was reading The Double Helix as a kid, 109 00:07:09,680 --> 00:07:12,560 Speaker 1: she was captivated not just by the discovery or even 110 00:07:12,600 --> 00:07:16,520 Speaker 1: the detective's tale, Isaacson says, but by one character in particular. 111 00:07:17,560 --> 00:07:21,360 Speaker 2: One of the interesting things about The Double Helix is 112 00:07:21,360 --> 00:07:25,480 Speaker 2: there's a character in it named Rosalind Franklin, very to 113 00:07:25,600 --> 00:07:29,560 Speaker 2: us and the science world famous because she takes the 114 00:07:29,600 --> 00:07:33,640 Speaker 2: photographs that allow Watson and Crick to figure out the 115 00:07:33,680 --> 00:07:37,320 Speaker 2: double helix structure of DNA, and she doesn't get much credit. 116 00:07:37,400 --> 00:07:41,800 Speaker 2: And in the book that Watson writes, he dismisses her 117 00:07:41,840 --> 00:07:44,680 Speaker 2: a bit. He calls her Rosie, even though he takes 118 00:07:44,680 --> 00:07:48,800 Speaker 2: her science seriously. And I asked Jennifer about that when 119 00:07:48,840 --> 00:07:51,520 Speaker 2: she read the book. Did she notice the dismissiveness. She 120 00:07:51,560 --> 00:07:55,880 Speaker 2: said no, because I was so surprised that a girl 121 00:07:55,920 --> 00:07:59,720 Speaker 2: could be a scientist. And that's what I took away 122 00:07:59,720 --> 00:08:03,840 Speaker 2: from book, was I did not know women were scientists, 123 00:08:03,880 --> 00:08:04,280 Speaker 2: so she. 124 00:08:04,240 --> 00:08:06,920 Speaker 1: Didn't find early in her life role models. 125 00:08:07,280 --> 00:08:10,520 Speaker 2: She said she had two role models. One was Russell 126 00:08:10,560 --> 00:08:13,240 Speaker 2: and Franklin in this book, and the other she read 127 00:08:13,280 --> 00:08:18,000 Speaker 2: a childhood book about Marie Curie. And she had always 128 00:08:18,040 --> 00:08:20,840 Speaker 2: wanted to be a French teacher, and she was doing 129 00:08:21,200 --> 00:08:25,600 Speaker 2: literature even in high school. And so she told her 130 00:08:25,640 --> 00:08:28,960 Speaker 2: guidance counselor at school, I think I want to be 131 00:08:29,000 --> 00:08:33,319 Speaker 2: a scientist. And the guidance counselor in Ilo, Hawaii said, no, 132 00:08:33,559 --> 00:08:37,240 Speaker 2: girls don't do science. Well, it was a good thing 133 00:08:37,360 --> 00:08:39,520 Speaker 2: that he said that, because if you know Jennifer and 134 00:08:39,559 --> 00:08:42,319 Speaker 2: you read the book, that's going to get her back up. 135 00:08:42,520 --> 00:08:45,480 Speaker 2: And it does, and she says, then I'm going to 136 00:08:45,520 --> 00:08:50,040 Speaker 2: become a scientist. She was very lucky to have a mentor. 137 00:08:50,559 --> 00:08:53,640 Speaker 2: There was a guy named Don Hemis who taught biology 138 00:08:53,720 --> 00:08:58,959 Speaker 2: at the local college in Helo of Hawaii, and he 139 00:08:59,000 --> 00:09:00,960 Speaker 2: would go on walks on the beach with her and 140 00:09:01,120 --> 00:09:05,960 Speaker 2: collect small organisms and show the crustaceans and how they 141 00:09:06,040 --> 00:09:09,880 Speaker 2: work and allowed her to indulge her interests in science, 142 00:09:10,200 --> 00:09:12,599 Speaker 2: and even in the summer, would bring her into the 143 00:09:12,720 --> 00:09:16,760 Speaker 2: lab where she could look at the shells under a microscope, 144 00:09:16,960 --> 00:09:21,520 Speaker 2: and we have to realize the importance of mentorship and 145 00:09:21,640 --> 00:09:27,000 Speaker 2: also realize that sometimes science is not something that everybody 146 00:09:27,000 --> 00:09:29,800 Speaker 2: gets to be a part of. There's a lot of 147 00:09:29,880 --> 00:09:33,160 Speaker 2: underrepresented groups in science, including women. 148 00:09:33,679 --> 00:09:36,240 Speaker 1: And it seems like she once she got to college, 149 00:09:36,800 --> 00:09:38,800 Speaker 1: she did start to you know, she had a real 150 00:09:38,840 --> 00:09:41,160 Speaker 1: aptitude for science, but even then she almost was a 151 00:09:41,200 --> 00:09:45,120 Speaker 1: French wanted to become an expert in French literature instead. 152 00:09:45,760 --> 00:09:48,679 Speaker 2: Yeah, she goes to Pomona, which has a great chemistry 153 00:09:48,679 --> 00:09:52,480 Speaker 2: department and a smaller college in California. She's really out 154 00:09:52,520 --> 00:09:55,839 Speaker 2: of place because you know, she's from Hawaii and I 155 00:09:55,840 --> 00:10:00,679 Speaker 2: don't know anybody, and she's finding the chemistry hard because 156 00:10:00,679 --> 00:10:04,560 Speaker 2: she didn't know enough math. And she tells her French 157 00:10:04,640 --> 00:10:07,920 Speaker 2: teacher at college, I think I'm going to change majors 158 00:10:08,040 --> 00:10:11,400 Speaker 2: to French. I've always wanted to be a French major. 159 00:10:12,120 --> 00:10:17,400 Speaker 2: And fortunately the French professor says something. She says, you know, 160 00:10:17,720 --> 00:10:20,240 Speaker 2: if you become a French major, that's great, and you 161 00:10:20,320 --> 00:10:23,360 Speaker 2: may become a French professor. But if you become a 162 00:10:23,400 --> 00:10:26,439 Speaker 2: biology major, there's probably more open to you. 163 00:10:27,440 --> 00:10:32,920 Speaker 1: It's true, it's true. The job prospects are significantly different. 164 00:10:32,960 --> 00:10:35,440 Speaker 1: So then she ends up at Harvard. She ends up 165 00:10:35,480 --> 00:10:39,400 Speaker 1: in Jack Shostak's lab, and this seems like another sort 166 00:10:39,440 --> 00:10:42,800 Speaker 1: of pivotal moment in the sense that he conveys to 167 00:10:42,800 --> 00:10:46,920 Speaker 1: her something about doing basic science and why you're doing 168 00:10:46,920 --> 00:10:49,360 Speaker 1: it and what you're trying to capture. 169 00:10:49,840 --> 00:10:53,360 Speaker 2: Two things. He conveys the importance of basic science. In 170 00:10:53,400 --> 00:10:55,440 Speaker 2: other words, you're not supposed to be just trying to 171 00:10:55,480 --> 00:10:59,800 Speaker 2: invent a new microchip or invent a gene editing tools, 172 00:11:00,360 --> 00:11:04,560 Speaker 2: to be marveling at the basic beauty of nature. And secondly, 173 00:11:04,600 --> 00:11:08,079 Speaker 2: he said, ask the big questions, and she said, what's 174 00:11:08,160 --> 00:11:11,360 Speaker 2: the big question? And he says, the origin of life? 175 00:11:11,800 --> 00:11:14,840 Speaker 2: How did it happen? And that's when they start looking 176 00:11:14,880 --> 00:11:17,920 Speaker 2: at RNA, a molecule that's not as famous as its 177 00:11:17,920 --> 00:11:18,800 Speaker 2: sibling DNA. 178 00:11:19,360 --> 00:11:21,720 Speaker 1: And in the book, you take us through some of 179 00:11:21,760 --> 00:11:24,440 Speaker 1: the history of how these discoveries were made, and we 180 00:11:24,480 --> 00:11:26,720 Speaker 1: don't have to go through the whole history of it. 181 00:11:26,800 --> 00:11:30,160 Speaker 1: But you know, Darwin to Gregor Mendel, oh, let's we can, 182 00:11:30,520 --> 00:11:31,280 Speaker 1: we certainly can. 183 00:11:31,800 --> 00:11:35,440 Speaker 2: Well, you gotta start with Darwin and Mendel, both in 184 00:11:35,520 --> 00:11:39,079 Speaker 2: the same periods on the mid eighteen hundreds, and what 185 00:11:39,440 --> 00:11:42,560 Speaker 2: Darwin figures out by going on the voyage of the 186 00:11:42,600 --> 00:11:47,520 Speaker 2: beagles of the Galapagos and others is different species adapt 187 00:11:47,880 --> 00:11:51,000 Speaker 2: as their environment changes. He looks at the beaks of 188 00:11:51,040 --> 00:11:53,800 Speaker 2: the finches and like, oh, maybe they had a drought 189 00:11:53,840 --> 00:11:56,440 Speaker 2: and the beak becomes something that can open up nuts. 190 00:11:56,840 --> 00:11:59,920 Speaker 2: So he's trying to figure out how does this information, 191 00:12:00,720 --> 00:12:05,920 Speaker 2: this survival of the fittest lead to changes in the 192 00:12:06,000 --> 00:12:10,520 Speaker 2: genetic information. And at the same time, unbeknownst to him, 193 00:12:10,800 --> 00:12:15,000 Speaker 2: there's a priest in Burno, which is the Czech Republic now, 194 00:12:15,679 --> 00:12:19,200 Speaker 2: who is breeding peas, and he would say, okay, I 195 00:12:19,400 --> 00:12:22,040 Speaker 2: like the peas with the purple coat, and when I 196 00:12:22,160 --> 00:12:24,600 Speaker 2: mix them with the piece with the white coat, they 197 00:12:24,600 --> 00:12:28,680 Speaker 2: don't sort of blend purple and white. They'll have a 198 00:12:28,760 --> 00:12:32,320 Speaker 2: dominant gene, so most turnout purple, but one will turn 199 00:12:32,360 --> 00:12:35,559 Speaker 2: out white in the second generation. So all of that 200 00:12:35,600 --> 00:12:40,160 Speaker 2: information comes together and they finally discover around nineteen hundred 201 00:12:40,679 --> 00:12:45,640 Speaker 2: there just must be some chemical in our body that 202 00:12:45,880 --> 00:12:51,360 Speaker 2: transmits this genetic information, and that's where the hunt begins 203 00:12:51,800 --> 00:12:54,720 Speaker 2: for how does genetic information get transmitted? 204 00:12:55,880 --> 00:12:58,280 Speaker 1: Coming up after the break, we dive into the human 205 00:12:58,320 --> 00:13:02,920 Speaker 1: genome project and why some scientists, notably women, didn't get 206 00:13:02,960 --> 00:13:03,880 Speaker 1: the chance to work on it. 207 00:13:15,960 --> 00:13:19,760 Speaker 2: The big breakthrough around nineteen fifty or so is when 208 00:13:19,840 --> 00:13:25,199 Speaker 2: James Watson and Francis Kraik get together in Cambridge University, 209 00:13:25,280 --> 00:13:30,200 Speaker 2: England and they figure out the DNS structure, which is 210 00:13:30,240 --> 00:13:35,040 Speaker 2: it has two strands and it's like a spiral staircase, 211 00:13:35,400 --> 00:13:39,360 Speaker 2: and the wrongs are four different letters we'll call out 212 00:13:39,640 --> 00:13:45,960 Speaker 2: chemicals ATCG and it can pull itself. It pulls apart 213 00:13:46,360 --> 00:13:50,760 Speaker 2: and replicates itself, and those letters three billion pairs of 214 00:13:50,800 --> 00:13:55,360 Speaker 2: code to code you and me that encodes the genetic 215 00:13:55,400 --> 00:13:58,760 Speaker 2: information that gets transferred generation to generation. 216 00:13:59,440 --> 00:14:02,280 Speaker 1: This string of findings from Darwin to Watson and Crick 217 00:14:02,760 --> 00:14:05,520 Speaker 1: with a foundation for the study of DNA. But fast 218 00:14:05,520 --> 00:14:08,240 Speaker 1: forward two decades later and Jennifer DOWDNA and our mentor 219 00:14:08,240 --> 00:14:11,920 Speaker 1: at Harvard, doctor Jack Showsteck, we're paying attention to another 220 00:14:11,960 --> 00:14:15,280 Speaker 1: important but more neglected molecule, RNA. 221 00:14:16,200 --> 00:14:20,240 Speaker 2: The different molecules we have in our body, proteins being 222 00:14:20,400 --> 00:14:24,040 Speaker 2: among the most famous, but there's also what they're called 223 00:14:24,120 --> 00:14:29,480 Speaker 2: nucleic acids, and they're two of them, RNA and DNA. 224 00:14:30,040 --> 00:14:35,840 Speaker 2: And DNA is what encodes our heredity, our genes. They 225 00:14:35,840 --> 00:14:40,040 Speaker 2: are encoded in this four letter code that can replicate 226 00:14:40,040 --> 00:14:43,000 Speaker 2: itself because the strands of DNA can pull apart and 227 00:14:43,040 --> 00:14:47,840 Speaker 2: then create an identical new set of DNA strands. That's 228 00:14:47,920 --> 00:14:52,880 Speaker 2: how we transmit genetic information. But the real question is 229 00:14:54,200 --> 00:14:58,000 Speaker 2: what makes that work, and that's what RNA does. It's 230 00:14:58,040 --> 00:15:01,360 Speaker 2: not as famous, but alike a lot of not famous siblings, 231 00:15:01,400 --> 00:15:04,800 Speaker 2: it actually does more work because the DNA just sits 232 00:15:04,840 --> 00:15:08,600 Speaker 2: there in the nucleus of your cell curating this information. 233 00:15:08,800 --> 00:15:13,160 Speaker 2: It can't go anywhere. He carefully guards it. But RNA 234 00:15:13,400 --> 00:15:18,440 Speaker 2: goes into the nucleus, reads that blueprint, reads that information 235 00:15:18,680 --> 00:15:21,680 Speaker 2: in the DNA code, and then goes to the outer 236 00:15:22,680 --> 00:15:26,800 Speaker 2: area of the cell where proteins are made, and it 237 00:15:26,880 --> 00:15:30,600 Speaker 2: will make a protein based on the information it got 238 00:15:30,720 --> 00:15:35,880 Speaker 2: from DNA. And that's all life is is proteins getting made. 239 00:15:36,320 --> 00:15:39,160 Speaker 2: Whether it's your fingernails, your hair, or the neurons in 240 00:15:39,200 --> 00:15:42,720 Speaker 2: your brain or the muscles that twitch, those are just 241 00:15:42,800 --> 00:15:48,200 Speaker 2: different forms of protein that use the code in our genes. 242 00:15:48,800 --> 00:15:51,600 Speaker 2: And it's RNA that says, all right, we're now going 243 00:15:51,680 --> 00:15:55,080 Speaker 2: to build a molecule that's a hair follicle. 244 00:15:56,240 --> 00:15:59,360 Speaker 1: In that lab, Downa and our colleagues were focused squarely 245 00:15:59,440 --> 00:16:00,960 Speaker 1: on RNA. 246 00:16:01,400 --> 00:16:05,160 Speaker 2: DNA knows how to replicate itself. That's its strong that's 247 00:16:05,160 --> 00:16:10,479 Speaker 2: why it's DNA. Rna they figured out could also replicate 248 00:16:10,560 --> 00:16:15,880 Speaker 2: itself and help create proteins, and so it could have 249 00:16:15,960 --> 00:16:22,080 Speaker 2: been the original molecule that gets life started. And indeed 250 00:16:22,240 --> 00:16:26,760 Speaker 2: they do a paper about self replicating RNA and set 251 00:16:26,800 --> 00:16:29,800 Speaker 2: the groundwork for which it's now called the RNA world, 252 00:16:30,240 --> 00:16:33,080 Speaker 2: which is how did life begin? Well, there was a 253 00:16:33,320 --> 00:16:35,720 Speaker 2: stew of a lot of chemicals and four of them 254 00:16:35,760 --> 00:16:40,680 Speaker 2: get together and they start replicating, and it made her 255 00:16:40,800 --> 00:16:44,320 Speaker 2: always want to look at basic science and the big 256 00:16:44,400 --> 00:16:45,320 Speaker 2: questions of life. 257 00:16:45,840 --> 00:16:48,480 Speaker 1: Is that the paper that landed her at Cold Spring 258 00:16:48,840 --> 00:16:51,520 Speaker 1: giving the talk at age twenty three. 259 00:16:51,800 --> 00:16:56,960 Speaker 2: Absolutely the research with Jack shaw Stack into the RNA 260 00:16:57,000 --> 00:17:01,040 Speaker 2: world and how you could have RNA replicate itself and 261 00:17:01,120 --> 00:17:05,520 Speaker 2: do all these amazing things. She gets invited by the 262 00:17:05,520 --> 00:17:08,680 Speaker 2: great James Watson, who's double Helix she had read as 263 00:17:08,720 --> 00:17:12,000 Speaker 2: a kid, to come to cold Spring Harbor Lab on 264 00:17:12,080 --> 00:17:16,959 Speaker 2: Long Island where they have scientific conferences because Jack Showstack 265 00:17:17,040 --> 00:17:21,160 Speaker 2: couldn't come, and so she gets to present their war 266 00:17:21,720 --> 00:17:25,680 Speaker 2: with James Watson sitting in the front row, and this 267 00:17:25,760 --> 00:17:27,440 Speaker 2: is a seminal experience for her. 268 00:17:28,000 --> 00:17:31,000 Speaker 1: Isaacson tells me that for DOWDNA, the Cold Spring Harbor 269 00:17:31,040 --> 00:17:33,959 Speaker 1: conference was not just a full circle moment, but a 270 00:17:34,000 --> 00:17:37,200 Speaker 1: signal that she was joining this historical chain of discovery, 271 00:17:37,800 --> 00:17:41,920 Speaker 1: a generational project aimed at ultimately unraveling how our genes work. 272 00:17:42,720 --> 00:17:45,280 Speaker 1: But Downa wasn't alone. There was an expanding group of 273 00:17:45,320 --> 00:17:48,560 Speaker 1: researchers who were turning their attention to RNA. It feels 274 00:17:48,600 --> 00:17:51,119 Speaker 1: like when DOWDNA is sort of starting to come of 275 00:17:51,160 --> 00:17:54,359 Speaker 1: age as a scientist, she's, you know, she's working in 276 00:17:54,400 --> 00:17:57,360 Speaker 1: different labs. There's this next big development going on, which 277 00:17:57,400 --> 00:17:59,400 Speaker 1: is the Human Genome Project, and that's sort of what's 278 00:17:59,440 --> 00:18:03,359 Speaker 1: hovering over everything, but she goes in a different direction. 279 00:18:03,480 --> 00:18:06,359 Speaker 1: Maybe you can explain what the Human Geno Project was 280 00:18:06,400 --> 00:18:09,720 Speaker 1: doing and why she kind of went the other way. 281 00:18:10,680 --> 00:18:14,320 Speaker 2: So in the nineteen fifties, when Watching and Krick discover 282 00:18:14,560 --> 00:18:19,160 Speaker 2: the structure of DNA, the hunt becomes, let's look at 283 00:18:19,200 --> 00:18:23,520 Speaker 2: each of those letters and decode where in our DNA 284 00:18:23,720 --> 00:18:27,679 Speaker 2: it codes for air height, whatever may be encoded for. 285 00:18:28,119 --> 00:18:31,679 Speaker 2: And that was called the Human Genome Project. Which is 286 00:18:31,920 --> 00:18:35,800 Speaker 2: map the human gene and one of the leaders was 287 00:18:35,880 --> 00:18:40,119 Speaker 2: James Watson, and Francis Crick was very involved too. It 288 00:18:40,320 --> 00:18:44,240 Speaker 2: culminated in the year two thousand. 289 00:18:44,000 --> 00:18:47,320 Speaker 4: More than a thousand re searches across six nations have 290 00:18:47,400 --> 00:18:52,080 Speaker 4: revealed nearly all three billion letters of our miraculous genetic code. 291 00:18:52,160 --> 00:18:55,879 Speaker 4: I congratulate all of you on the stunning and humbling achievement. 292 00:18:57,240 --> 00:19:00,639 Speaker 2: I was at Time magazine and we put Francis Collins 293 00:19:01,320 --> 00:19:05,199 Speaker 2: and Craig Ventnor on the cover. They were rivals trying 294 00:19:05,240 --> 00:19:08,400 Speaker 2: to decode the gene. We were going to just do 295 00:19:08,480 --> 00:19:11,520 Speaker 2: Craig Ventor. The little thing was that the vice president 296 00:19:11,600 --> 00:19:14,520 Speaker 2: was Al Gore, and he was insistent. He even called 297 00:19:14,560 --> 00:19:17,840 Speaker 2: and said, you also have to put the National Institutes 298 00:19:17,880 --> 00:19:21,560 Speaker 2: of Health person, the government person. Yeah, he called and said, 299 00:19:21,960 --> 00:19:26,199 Speaker 2: you can't just put this privateer who's doing it. And 300 00:19:26,280 --> 00:19:28,520 Speaker 2: so we put them both on the cover, and we 301 00:19:28,560 --> 00:19:30,240 Speaker 2: thought it was the biggest thing in the world, that 302 00:19:30,720 --> 00:19:33,760 Speaker 2: all of human life would now change because we could 303 00:19:33,760 --> 00:19:38,600 Speaker 2: read the blueprint of the discovery of our human genome. 304 00:19:38,920 --> 00:19:41,560 Speaker 2: It was a big deal back then, and Dolly the 305 00:19:41,640 --> 00:19:45,919 Speaker 2: sheep was being cloned and everybody thought that DNA was 306 00:19:46,040 --> 00:19:50,320 Speaker 2: going to be a revolution, and like a lot of revolutions, 307 00:19:50,880 --> 00:19:55,840 Speaker 2: it actually started slowly. Why because we could now read 308 00:19:56,320 --> 00:19:59,240 Speaker 2: the code of life, but we couldn't do anything with it. 309 00:19:59,359 --> 00:20:01,720 Speaker 2: You couldn't re write it, you couldn't edit it. 310 00:20:02,359 --> 00:20:05,600 Speaker 1: But there was this sense then that well, now we 311 00:20:05,680 --> 00:20:06,920 Speaker 1: have command of this thing. 312 00:20:07,000 --> 00:20:07,320 Speaker 2: We know. 313 00:20:07,960 --> 00:20:09,760 Speaker 1: Now, we'll just figure out what all the genes do, 314 00:20:10,440 --> 00:20:13,040 Speaker 1: and then we'll be able to manipulate them. Down the line, 315 00:20:13,040 --> 00:20:16,200 Speaker 1: we'll be able to cure diseases. But everyone was forgetting 316 00:20:16,200 --> 00:20:18,879 Speaker 1: about another element, which was RNA. 317 00:20:19,840 --> 00:20:22,440 Speaker 2: It was quite nice to be able to say, oh, 318 00:20:22,480 --> 00:20:25,280 Speaker 2: that's the part of the gene that does this, but 319 00:20:25,400 --> 00:20:28,160 Speaker 2: let's say it's the letter in the gene that's messed 320 00:20:28,240 --> 00:20:33,280 Speaker 2: up that causes sickle cell anemia. That was fine to know, 321 00:20:33,600 --> 00:20:37,640 Speaker 2: but there wasn't much useful that came out of it. 322 00:20:38,119 --> 00:20:42,000 Speaker 2: And that's when RNA and the women who were focusing 323 00:20:42,040 --> 00:20:45,320 Speaker 2: on RNA entered the story. One of the things that 324 00:20:45,400 --> 00:20:49,159 Speaker 2: happened is the Human Genome Project. In decoding DNA is 325 00:20:49,560 --> 00:20:53,879 Speaker 2: mainly an alpha male exercise. Jennifer Dowd and when she 326 00:20:54,040 --> 00:20:57,000 Speaker 2: played soccer as a little kid in Hawaii, she said, 327 00:20:57,040 --> 00:20:59,480 Speaker 2: all the boys used to run to the ball, but 328 00:20:59,560 --> 00:21:02,359 Speaker 2: I always wanted to run to where the ball was 329 00:21:02,400 --> 00:21:05,040 Speaker 2: going to be. And so a lot of women who 330 00:21:05,040 --> 00:21:09,920 Speaker 2: were not part of the Human Genome Project started studying RNA, 331 00:21:10,400 --> 00:21:15,520 Speaker 2: the less famous molecule, and those were people like Jillian Vanfield, 332 00:21:15,840 --> 00:21:21,919 Speaker 2: Emmanuel Scharpancha, Katti Carichko, and of course Jennifer Daudna. In 333 00:21:21,960 --> 00:21:24,600 Speaker 2: the end, it turns out that RNA is a lot 334 00:21:24,720 --> 00:21:28,640 Speaker 2: more useful to understand because it's the one that goes 335 00:21:28,680 --> 00:21:32,199 Speaker 2: and does work, reads the DNA, and then has the 336 00:21:32,240 --> 00:21:35,360 Speaker 2: protein made. It's also can be a messenger to make 337 00:21:35,400 --> 00:21:38,320 Speaker 2: any protein you want, which is quite useful when you're 338 00:21:38,320 --> 00:21:41,080 Speaker 2: trying to invent a COVID vaccine and you want to 339 00:21:41,119 --> 00:21:46,320 Speaker 2: make a fake spike protein in people's cells. So a 340 00:21:46,359 --> 00:21:51,200 Speaker 2: lot of women were doing RNA, and after the Human 341 00:21:51,240 --> 00:21:55,320 Speaker 2: Genome Project, it became important to say, well, what are 342 00:21:55,320 --> 00:21:57,639 Speaker 2: we going to do with all this information. We have 343 00:21:57,680 --> 00:21:59,560 Speaker 2: to be able to manipulate it, we have to edit it, 344 00:21:59,600 --> 00:22:02,280 Speaker 2: we have to do things with it. And that's where 345 00:22:02,480 --> 00:22:05,960 Speaker 2: RNA becomes the tool. Just like in our body, it's 346 00:22:06,000 --> 00:22:10,679 Speaker 2: a tool for applying the code of DNA to the 347 00:22:10,680 --> 00:22:15,680 Speaker 2: making of protein. In science and the basic research. It 348 00:22:15,840 --> 00:22:19,800 Speaker 2: becomes the tool for understanding what we can do with 349 00:22:19,880 --> 00:22:20,959 Speaker 2: our genetic coding. 350 00:22:21,359 --> 00:22:23,840 Speaker 1: Isaacson says that in order to really understand how to 351 00:22:23,880 --> 00:22:27,199 Speaker 1: harness the abilities of RNA, Jennifer Downer realized that she 352 00:22:27,240 --> 00:22:29,359 Speaker 1: had to use some of the same techniques deployed by 353 00:22:29,440 --> 00:22:33,760 Speaker 1: Roslin Franklin to uncover the structure of DNA, namely an 354 00:22:33,800 --> 00:22:38,680 Speaker 1: imaging technology called X ray crystallography, which, as Isaacson writes, 355 00:22:38,920 --> 00:22:41,480 Speaker 1: she could use to figure out the folds and twists 356 00:22:41,640 --> 00:22:44,360 Speaker 1: of the three dimensional structure of self splicing RNA. 357 00:22:44,840 --> 00:22:49,480 Speaker 2: She had understood from Jack show Stack the importance of 358 00:22:49,600 --> 00:22:54,320 Speaker 2: RNA and how RNA explained the origins of life. So 359 00:22:54,400 --> 00:22:58,399 Speaker 2: she's doing things about the structure of RNA, trying to 360 00:22:58,480 --> 00:23:01,679 Speaker 2: crystallize it. That's the way scientists are able to figure 361 00:23:01,680 --> 00:23:04,320 Speaker 2: out what does it really look like? You know? How 362 00:23:04,320 --> 00:23:07,280 Speaker 2: can I shine light into it? Is what Rosalind Franklin 363 00:23:07,359 --> 00:23:10,600 Speaker 2: did for DNA, so that we can see the structure 364 00:23:10,640 --> 00:23:11,360 Speaker 2: in the shape. 365 00:23:11,520 --> 00:23:14,879 Speaker 1: Mm hmm. And it seems like Jennifer Downas she really 366 00:23:15,000 --> 00:23:18,200 Speaker 1: she had that maybe that soccer player moving to where 367 00:23:18,240 --> 00:23:20,800 Speaker 1: the ball is going to be sense of there's something 368 00:23:20,880 --> 00:23:24,640 Speaker 1: here that we're going to need to know, and there's 369 00:23:24,720 --> 00:23:26,600 Speaker 1: basic science to be done here. And I feel like 370 00:23:26,760 --> 00:23:29,240 Speaker 1: her first the first time she sort of has a 371 00:23:29,280 --> 00:23:32,679 Speaker 1: public profile, is like a little story that you found. 372 00:23:32,800 --> 00:23:35,080 Speaker 1: When she's at Yale. She's working on the structure of 373 00:23:35,200 --> 00:23:39,240 Speaker 1: RNA and there's a very moving scene where she's trying 374 00:23:39,240 --> 00:23:42,600 Speaker 1: to resolve this question and her father is dying. At 375 00:23:42,600 --> 00:23:44,080 Speaker 1: the same time, her. 376 00:23:43,880 --> 00:23:47,000 Speaker 2: Father was dying, and her father was this great influence. 377 00:23:47,040 --> 00:23:49,960 Speaker 2: It always pushed her to be a scientist, and he 378 00:23:50,040 --> 00:23:53,160 Speaker 2: kept saying, even though he was fighting cancer, kept saying, 379 00:23:53,200 --> 00:23:56,399 Speaker 2: explain it to me. Explain what you're doing. And that 380 00:23:56,520 --> 00:24:01,000 Speaker 2: becomes one of Jennifer down his superpowers is being able 381 00:24:01,040 --> 00:24:03,680 Speaker 2: to explain what was happening. 382 00:24:05,160 --> 00:24:07,639 Speaker 1: What she explained to her father was her first taste 383 00:24:07,640 --> 00:24:11,320 Speaker 1: of real scientific discovery, a picture of the three dimensional 384 00:24:11,320 --> 00:24:14,960 Speaker 1: folded shape of an RNA molecule. But for DOWDNA and 385 00:24:14,960 --> 00:24:18,280 Speaker 1: her expanding orbit of colleagues, kneeling the structure of RNA 386 00:24:18,400 --> 00:24:21,159 Speaker 1: was just the beginning. To figure out how to harness 387 00:24:21,160 --> 00:24:23,760 Speaker 1: that structure, she would need to piggyback on an obscure 388 00:24:23,840 --> 00:24:26,960 Speaker 1: breakthrough from across the ocean in Spain. 389 00:24:28,359 --> 00:24:33,800 Speaker 2: A graduate student, young scientist in Spain and he's looking 390 00:24:33,880 --> 00:24:40,639 Speaker 2: at bacteria in very, very salty ponds and he notices 391 00:24:40,720 --> 00:24:44,720 Speaker 2: something when he's sequencing the genes, and he keeps seeing 392 00:24:45,200 --> 00:24:51,159 Speaker 2: these repeated sequences, but nobody knows why they exist, and 393 00:24:51,240 --> 00:24:52,560 Speaker 2: that's when the hunt begins. 394 00:24:53,720 --> 00:24:56,160 Speaker 1: Coming out this season on Crisper. 395 00:24:56,240 --> 00:25:00,960 Speaker 2: There's a race around the world. It's dangerous because scientists 396 00:25:00,960 --> 00:25:04,919 Speaker 2: are sometimes competitive. They want to get their paper published first. 397 00:25:05,400 --> 00:25:07,440 Speaker 2: They want to win the prize, they want to get 398 00:25:07,440 --> 00:25:11,040 Speaker 2: the patent. Not only will we be able to cut 399 00:25:11,160 --> 00:25:14,320 Speaker 2: DNA will cut and paste just as if we were 400 00:25:14,400 --> 00:25:19,760 Speaker 2: using a word processor. Jennifer had a nightmare and it 401 00:25:19,960 --> 00:25:23,720 Speaker 2: was that somebody wanted to meet with her about this 402 00:25:23,840 --> 00:25:27,040 Speaker 2: new technology. And she opens the door to the room. 403 00:25:27,240 --> 00:25:32,080 Speaker 2: The person looks up and it's Adolph Hitler, and she's 404 00:25:32,160 --> 00:25:37,000 Speaker 2: taken aback and she realizes, of course, that in the 405 00:25:37,080 --> 00:25:43,959 Speaker 2: wrong hands, this tool could be not just powerful, but evil. 406 00:25:46,080 --> 00:25:48,479 Speaker 1: On Crisper, The Story of Jennifer DOWDNA is a production 407 00:25:48,520 --> 00:25:51,320 Speaker 1: of Kaleidoscope and iHeart. This show is based on the 408 00:25:51,320 --> 00:25:54,199 Speaker 1: writing and reporting of Walter Isaacson. It's hosted by me 409 00:25:54,240 --> 00:25:57,120 Speaker 1: Evan Ratliff and produced by Adrianna Tapia with assistance from 410 00:25:57,160 --> 00:26:00,199 Speaker 1: Alex Zonaveld's. It was mixed by Kyle Murdoch and our 411 00:26:00,240 --> 00:26:03,560 Speaker 1: studio engineer was Thomas Walsh. Our executive producers are Kate 412 00:26:03,560 --> 00:26:07,960 Speaker 1: Osbourne and Mangashatigador from Kalidoscope and Katrina Norvell from iHeart Podcasts. 413 00:26:08,200 --> 00:26:11,119 Speaker 1: If you enjoy hearing stories about visionaries and science and technology, 414 00:26:11,400 --> 00:26:13,560 Speaker 1: check out our other seasons. Bates on the biographies that 415 00:26:13,560 --> 00:26:17,000 Speaker 1: Walter Isaacson's written, on Musk for an intimate dive into 416 00:26:17,040 --> 00:26:20,120 Speaker 1: all the facets of Elon Musk, and on Benjamin Franklin 417 00:26:20,280 --> 00:26:23,600 Speaker 1: to understand how his scientific curiosity shapes society as we 418 00:26:23,680 --> 00:26:25,159 Speaker 1: know it. Thanks for listening.