WEBVTT 00:00:00.000 --> 00:00:02.000 Welcome to the Deep Dive, where we take the most 00:00:02.000 --> 00:00:05.099 complex research articles and scientific profiles 00:00:05.099 --> 00:00:07.980 and really distill the knowledge you need to 00:00:07.980 --> 00:00:10.779 be well -informed. And today we are wrestling 00:00:10.779 --> 00:00:13.320 with a topic that, well, it sounds like something 00:00:13.320 --> 00:00:15.119 straight out of science fiction. It really does. 00:00:15.240 --> 00:00:17.480 We're talking about the ability to precisely 00:00:17.480 --> 00:00:21.899 edit the foundational code of life. I mean, rewriting 00:00:21.899 --> 00:00:25.039 the very blueprints of existence in any organism 00:00:25.039 --> 00:00:27.690 on Earth. It's a monumental shift. You know, 00:00:27.690 --> 00:00:29.570 for decades, science was all about reading the 00:00:29.570 --> 00:00:32.630 genome. Now we have the ability to go in and 00:00:32.630 --> 00:00:35.490 write new sections, correct errors, even delete 00:00:35.490 --> 00:00:37.950 entire passages. And the figure right at the 00:00:37.950 --> 00:00:39.990 center of this revolution is Jennifer Doudna. 00:00:40.130 --> 00:00:42.789 Her journey is just as fascinating as the technology 00:00:42.789 --> 00:00:45.289 she helped create. Absolutely. So our deep dive 00:00:45.289 --> 00:00:47.210 today is built around a really comprehensive 00:00:47.210 --> 00:00:49.810 look at Doudna's career. And we're not just focusing 00:00:49.810 --> 00:00:52.810 on the 2020 Nobel Prize she won for CRISPR -Cas9 00:00:52.810 --> 00:00:54.750 genome editing. No, we have to go back further. 00:00:55.079 --> 00:00:56.579 We're going all the way back to her origins, 00:00:56.759 --> 00:00:59.240 this inquisitive kid in Hawaii, the structural 00:00:59.240 --> 00:01:02.700 biologist obsessed with complex RNA shapes to 00:01:02.700 --> 00:01:06.840 really understand. the often overlooked foundational 00:01:06.840 --> 00:01:09.620 work that made all of this possible. Our mission 00:01:09.620 --> 00:01:11.659 for you, the listener, is really to connect the 00:01:11.659 --> 00:01:13.959 dots. You need to understand the molecular mechanics 00:01:13.959 --> 00:01:17.920 of how this technology works, the high -stakes 00:01:17.920 --> 00:01:20.480 legal battles over its ownership, and the ambitious 00:01:20.480 --> 00:01:23.459 ethical framework Doudna is building to ensure 00:01:23.459 --> 00:01:26.379 this powerful tool is used responsibly. We're 00:01:26.379 --> 00:01:29.019 tracing a whole scientific lifetime from the 00:01:29.019 --> 00:01:31.780 lab bench to the Nobel stage and way beyond. 00:01:32.000 --> 00:01:34.659 Our goal is to make sure you walk away understanding 00:01:34.659 --> 00:01:37.359 not just the what of CRISPR, but the deeper how 00:01:37.359 --> 00:01:39.700 and why it matters for all of us. So let's get 00:01:39.700 --> 00:01:41.680 started. Let's unpack this journey, starting 00:01:41.680 --> 00:01:43.980 with her earliest inspirations. You know, it's 00:01:43.980 --> 00:01:45.560 so important to start with the environment that 00:01:45.560 --> 00:01:48.120 shaped her curiosity. Doudna was born in Washington, 00:01:48.280 --> 00:01:50.739 D .C., but her formative years, they really began 00:01:50.739 --> 00:01:53.480 when her family moved to Hulo, Hawaii. She was 00:01:53.480 --> 00:01:56.299 seven years old. And Hilo is such a specific, 00:01:56.459 --> 00:01:59.299 vibrant place. You can't live there without being 00:01:59.299 --> 00:02:02.540 just immersed in this unique, lush biodiversity. 00:02:03.000 --> 00:02:05.560 Exactly. The source material really highlights 00:02:05.560 --> 00:02:08.379 that this upbringing fostered a deep intrinsic 00:02:08.379 --> 00:02:12.599 fascination with the local flora and fauna. I 00:02:12.599 --> 00:02:14.520 mean, it's hard to imagine a better incubator 00:02:14.520 --> 00:02:17.020 for someone who would dedicate her life to understanding 00:02:17.020 --> 00:02:19.680 the mechanisms of biological systems. And her 00:02:19.680 --> 00:02:22.060 parents were a huge intellectual influence. Her 00:02:22.060 --> 00:02:24.159 father had a Ph .D. in English literature and 00:02:24.159 --> 00:02:26.840 her mother, who taught history, held two master's 00:02:26.840 --> 00:02:28.979 degrees. So the home environment was clearly 00:02:28.979 --> 00:02:31.719 one that valued learning and, you know, intellectual 00:02:31.719 --> 00:02:35.060 pursuit. But the real spark, the defining moment 00:02:35.060 --> 00:02:37.500 that came in the sixth grade. Right. This is 00:02:37.500 --> 00:02:39.280 the moment that's almost legendary in scientific 00:02:39.280 --> 00:02:41.860 biographies now. It's when her father handed 00:02:41.860 --> 00:02:45.219 her a copy of James Watson's 1968 book, The Double 00:02:45.219 --> 00:02:48.500 Helix. A powerful gift. I mean, that book, which 00:02:48.500 --> 00:02:51.740 recounts the thrilling, sometimes messy discovery 00:02:51.740 --> 00:02:54.879 of the structure of DNA. It was a profound inspiration 00:02:54.879 --> 00:02:57.560 for her. It introduced her to the idea that life 00:02:57.560 --> 00:02:59.439 itself could be understood through molecular 00:02:59.439 --> 00:03:02.419 structure, that there was a blueprint. And it's 00:03:02.419 --> 00:03:05.259 incredible to think of a sixth grader being captivated 00:03:05.259 --> 00:03:07.639 by that, by the molecular structure of existence. 00:03:08.060 --> 00:03:10.580 And that seed of curiosity was then nurtured 00:03:10.580 --> 00:03:13.939 by some really excellent mentorship. Her 10th 00:03:13.939 --> 00:03:16.219 grade chemistry teacher at Hilo High School, 00:03:16.379 --> 00:03:19.280 a woman named Jeanette Wong, is cited as a major 00:03:19.280 --> 00:03:22.569 influence. Right. She transformed that nascent 00:03:22.569 --> 00:03:25.729 interest into a really focused curiosity. We 00:03:25.729 --> 00:03:27.770 can't overlook the power of those early teachers. 00:03:28.169 --> 00:03:31.090 There was also an encouraging lecture on cancer 00:03:31.090 --> 00:03:33.590 cells that sort of reinforced her career path. 00:03:33.810 --> 00:03:36.449 But even with all of this early momentum, her 00:03:36.449 --> 00:03:38.650 confidence wavered when she got to Pomona College 00:03:38.650 --> 00:03:41.710 to study biochemistry. A completely relatable 00:03:41.710 --> 00:03:44.370 moment of doubt, right? Totally. Our sources 00:03:44.370 --> 00:03:46.490 reveal that during her freshman year, Doudna 00:03:46.490 --> 00:03:48.409 actually considered dropping science entirely. 00:03:48.729 --> 00:03:51.270 She wanted to switch her major to French. She 00:03:51.270 --> 00:03:53.530 felt overwhelmed by the difficulty of the general 00:03:53.530 --> 00:03:56.169 chemistry classes. But here's the twist. It was 00:03:56.169 --> 00:03:58.409 her French teacher who encouraged her to stick 00:03:58.409 --> 00:04:01.169 with science. It's a remarkable little historical 00:04:01.169 --> 00:04:04.050 footnote, isn't it? A single conversation that 00:04:04.050 --> 00:04:06.569 may have prevented a Nobel Prize winning scientist 00:04:06.569 --> 00:04:10.139 from changing fields entirely. So she overcame 00:04:10.139 --> 00:04:12.360 that self -doubt and graduated with her Bachelor 00:04:12.360 --> 00:04:15.319 of Arts in Biochemistry in 1985. From there, 00:04:15.400 --> 00:04:18.579 the specialization really begins. She chose Harvard 00:04:18.579 --> 00:04:20.879 Medical School for her doctoral studies, completing 00:04:20.879 --> 00:04:23.480 her PhD in Biological Chemistry and Molecular 00:04:23.480 --> 00:04:26.459 Pharmacology in 1989. And she was working under 00:04:26.459 --> 00:04:29.420 the renowned Jack Sostak. Yes. And this is where 00:04:29.420 --> 00:04:32.459 her focus on nucleic acids truly locks in, but 00:04:32.459 --> 00:04:35.279 in a very, very specific way. Her dissertation 00:04:35.279 --> 00:04:38.379 wasn't just about DNA or RNA as, you know, information 00:04:38.379 --> 00:04:41.699 storage. It was focused on increasing the efficiency 00:04:41.699 --> 00:04:44.959 of a self -replicating catalytic RNA. That distinction 00:04:44.959 --> 00:04:48.019 catalytic RNA is so key to understanding her 00:04:48.019 --> 00:04:50.769 entire career trajectory. It's everything. For 00:04:50.769 --> 00:04:52.350 our listeners who might be familiar with basic 00:04:52.350 --> 00:04:55.129 biology, we typically think of RNA as a messenger, 00:04:55.250 --> 00:04:58.189 right? It carries instructions from DNA to the 00:04:58.189 --> 00:05:00.569 protein -making machinery. And we think of proteins 00:05:00.569 --> 00:05:03.029 as the workers, the enzymes, that perform all 00:05:03.029 --> 00:05:05.250 the actual labor like catalyzing chemical reactions. 00:05:05.629 --> 00:05:08.189 Exactly. But Donau was focused on ribozymes. 00:05:08.310 --> 00:05:11.129 Right. RNA molecules that act as enzymes themselves, 00:05:11.449 --> 00:05:14.360 performing catalytic work. Her early dedication 00:05:14.360 --> 00:05:16.980 was to understanding RNA not just as a passive 00:05:16.980 --> 00:05:19.540 instruction manual, but as an active 3D functional 00:05:19.540 --> 00:05:22.399 machine. So this intellectual foundation is really 00:05:22.399 --> 00:05:25.379 the unheralded precursor to the CRISPR breakthrough 00:05:25.379 --> 00:05:28.800 years later. It absolutely is. She was already 00:05:28.800 --> 00:05:31.199 treating RNA as a potential tool long before 00:05:31.199 --> 00:05:34.100 Cass and I ever came along. That sets us up perfectly 00:05:34.100 --> 00:05:37.000 for the next phase of her career. She knew RNA 00:05:37.000 --> 00:05:39.519 could perform this complex work, but she needed 00:05:39.519 --> 00:05:41.980 to figure out how. How was it structured to do 00:05:41.980 --> 00:05:44.920 that work? So when Doudna began her postdoctoral 00:05:44.920 --> 00:05:47.839 work, the fundamental challenge facing her and 00:05:47.839 --> 00:05:50.079 really the entire molecular biology community 00:05:50.079 --> 00:05:53.120 was visualization. Right. These complex RNA enzymes, 00:05:53.360 --> 00:05:55.959 these ribozymes, and scientists could measure 00:05:55.959 --> 00:05:57.860 their catalytic activity, see what they did, 00:05:57.980 --> 00:05:59.839 but they couldn't see their internal mechanics. 00:06:00.160 --> 00:06:02.459 She realized she couldn't fully understand the 00:06:02.459 --> 00:06:04.420 function without actually seeing their three 00:06:04.420 --> 00:06:06.759 -dimensional structure. It's like trying to understand 00:06:06.759 --> 00:06:10.040 how a watch works just by listening to it tick. 00:06:10.199 --> 00:06:12.449 That's a great analogy. Yeah. have to open the 00:06:12.449 --> 00:06:15.170 case. And this challenge led her to the lab of 00:06:15.170 --> 00:06:17.410 Thomas Scheck at the University of Colorado Boulder 00:06:17.410 --> 00:06:21.089 starting in 1991. And Scheck himself was a Nobel 00:06:21.089 --> 00:06:23.470 laureate for identifying catalytic RNA in the 00:06:23.470 --> 00:06:25.050 first place, so she was going to the source. 00:06:25.230 --> 00:06:28.509 And her goal was monumental, to crystallize and 00:06:28.509 --> 00:06:30.990 determine the 3D structure of a ribozyme for 00:06:30.990 --> 00:06:33.750 the first time. So why was solving the structure 00:06:33.750 --> 00:06:38.170 of a ribozyme so crucial? Why spend years on 00:06:38.170 --> 00:06:41.410 this painstaking, difficult work? It was crucial 00:06:41.410 --> 00:06:43.769 to answer a really deep biological question. 00:06:44.069 --> 00:06:47.050 How similar or different are RNA -based catalysts 00:06:47.050 --> 00:06:49.870 to protein -based catalysts? Okay. I mean, if 00:06:49.870 --> 00:06:52.750 RNA performed the same duties as proteins, scientists 00:06:52.750 --> 00:06:55.350 needed to see how it folded and how it achieved 00:06:55.350 --> 00:06:58.110 chemical specificity. We needed to know if nature 00:06:58.110 --> 00:07:00.350 had evolved completely distinct structural rules 00:07:00.350 --> 00:07:03.149 for the two types of biological workers. And 00:07:03.149 --> 00:07:05.410 the technique you have to use to see these molecules 00:07:05.410 --> 00:07:08.029 is notoriously difficult, right? Roman, X -ray 00:07:08.029 --> 00:07:10.230 crystallography. Can you just give us a conceptual 00:07:10.230 --> 00:07:13.829 idea of how that process works? I can try. X 00:07:13.829 --> 00:07:15.629 -ray crystallography is essentially molecular 00:07:15.629 --> 00:07:18.430 photography. But instead of using visible light, 00:07:18.569 --> 00:07:21.550 you use X -rays. And first, you have to coax 00:07:21.550 --> 00:07:24.350 the molecule, in this case, a complex floppy 00:07:24.350 --> 00:07:28.029 RNA strand, to arrange itself into a highly ordered 00:07:28.029 --> 00:07:32.180 three -dimensional crystal. Which sounds... It's 00:07:32.180 --> 00:07:34.420 incredibly difficult. That process alone can 00:07:34.420 --> 00:07:37.120 take months or even years, especially for RNA, 00:07:37.339 --> 00:07:39.759 because it's often much more flexible than the 00:07:39.759 --> 00:07:42.180 rigid, well -behaved protein molecules scientists 00:07:42.180 --> 00:07:43.879 were used to working with. So once you have a 00:07:43.879 --> 00:07:45.920 crystal, if you can get one... If you get one, 00:07:46.019 --> 00:07:48.660 you bombard it with high -powered X -rays. As 00:07:48.660 --> 00:07:51.060 the X -rays pass through, they diffract or scatter 00:07:51.060 --> 00:07:53.879 off the atoms in the crystal. You capture the 00:07:53.879 --> 00:07:56.620 resulting pattern of dots on a detector and then... 00:07:56.920 --> 00:07:59.000 Then you use complex mathematical algorithms 00:07:59.000 --> 00:08:01.339 to reverse engineer the exact location of every 00:08:01.339 --> 00:08:03.420 single atom in that molecule. So it's a process 00:08:03.420 --> 00:08:05.939 that requires massive computational power and 00:08:05.939 --> 00:08:08.740 critically, extremely bright X -ray beams. Yes, 00:08:08.759 --> 00:08:10.680 which is why the move she made later in her career 00:08:10.680 --> 00:08:13.079 was so strategic. But the initial breakthrough, 00:08:13.240 --> 00:08:15.300 that happened at Yale. She established her first 00:08:15.300 --> 00:08:17.839 independent lab there, running from 1994 to 1996. 00:08:18.720 --> 00:08:20.839 This is the quiet foundational moment, right? 00:08:20.920 --> 00:08:23.019 The work that doesn't get the headlines but earned 00:08:23.019 --> 00:08:26.339 her scientific credentials. Precisely. Her team 00:08:26.339 --> 00:08:28.899 succeeded in solving the 3D structure of the 00:08:28.899 --> 00:08:32.320 catalytic core of the tetrahymena group R -rebozyme. 00:08:32.759 --> 00:08:35.240 This structure was the first complete blueprint 00:08:35.240 --> 00:08:38.659 of a major RNA enzyme. And this is where we need 00:08:38.659 --> 00:08:41.039 to dive into the specific molecular nugget that, 00:08:41.120 --> 00:08:44.059 you know, fundamentally changed the field. What 00:08:44.059 --> 00:08:47.220 did they actually find inside this complex RNA 00:08:47.220 --> 00:08:50.429 fold? What they found was a highly ordered specific 00:08:50.429 --> 00:08:53.750 cluster of five magnesium ions, and they were 00:08:53.750 --> 00:08:55.889 tucked deep inside the core of the molecule. 00:08:56.210 --> 00:08:58.610 Magnesium ions? Yeah. These magnesium ions were 00:08:58.610 --> 00:09:01.049 located within a specific domain of the ribozyme 00:09:01.049 --> 00:09:03.610 structure, and they were indispensable for the 00:09:03.610 --> 00:09:05.649 overall folding and stability of the molecule. 00:09:05.909 --> 00:09:08.240 Wait a minute. We always hear about the hydrophobic 00:09:08.240 --> 00:09:11.399 core being crucial for protein folding. Proteins 00:09:11.399 --> 00:09:13.980 achieve stability by burying water -repelling 00:09:13.980 --> 00:09:15.960 amino acids in their center, isn't that right? 00:09:16.200 --> 00:09:18.200 That's the traditional rule for proteins, yes. 00:09:18.419 --> 00:09:20.279 That's how they stabilize their complex shapes. 00:09:20.879 --> 00:09:23.659 But Doudna's team showed that this cluster of 00:09:23.659 --> 00:09:26.259 five magnesium ions was performing an analogous 00:09:26.259 --> 00:09:28.899 role for RNA. How so? Well, these positively 00:09:28.899 --> 00:09:32.200 charged metal ions organize the negatively charged 00:09:32.200 --> 00:09:35.220 phosphate backbone of the RNA, effectively allowing 00:09:35.220 --> 00:09:38.059 the molecule to fold into this complex, stable 00:09:38.059 --> 00:09:42.389 3D shape. So RNA uses ions in organic chemistry 00:09:42.389 --> 00:09:45.549 to create a core that functions structurally, 00:09:45.629 --> 00:09:48.690 like the organic hydrophobic cores of proteins. 00:09:48.809 --> 00:09:50.669 It's a completely different chemical trick to 00:09:50.669 --> 00:09:52.309 achieve the same sophisticated architecture. 00:09:52.649 --> 00:09:54.870 Wow. It showed that RNA has its own intricate, 00:09:54.929 --> 00:09:57.470 specific rules for self -assembly and catalysis. 00:09:57.669 --> 00:10:00.590 It's distinct from proteins, but equally capable 00:10:00.590 --> 00:10:04.049 of achieving complex functional folding. This 00:10:04.049 --> 00:10:05.850 wasn't just a pretty picture. It was a realization 00:10:05.850 --> 00:10:08.289 that RNA was a powerful, independent architect 00:10:08.289 --> 00:10:11.120 of life. And this success immediately established 00:10:11.120 --> 00:10:13.620 her expertise in structural biology. It did. 00:10:13.759 --> 00:10:16.379 It led to further work on other critical ribozymes, 00:10:16.440 --> 00:10:18.899 like the hepatitis delta virus ribozyme, and 00:10:18.899 --> 00:10:21.100 larger complexes such as the signal recumission 00:10:21.100 --> 00:10:23.559 particle. So her need for even higher resolution 00:10:23.559 --> 00:10:26.299 imagery and more intense X -ray beams prompted 00:10:26.299 --> 00:10:30.429 her move. Exactly. In 2002, she joined UC Berkeley, 00:10:30.710 --> 00:10:33.230 gaining access to the powerful synchrotron at 00:10:33.230 --> 00:10:35.950 Lawrence Berkeley National Laboratory. This was 00:10:35.950 --> 00:10:38.210 a critical step. A synchrotron is essentially 00:10:38.210 --> 00:10:41.590 a massive particle accelerator that creates X 00:10:41.590 --> 00:10:44.250 -rays bright enough to produce the high resolution 00:10:44.250 --> 00:10:47.149 diffraction patterns needed to map these incredibly 00:10:47.149 --> 00:10:50.330 dense structures. So by 2006, when the CRISPR 00:10:50.330 --> 00:10:53.169 story really starts, she isn't just a smart scientist. 00:10:53.309 --> 00:10:55.710 She's one of the world's foremost experts in 00:10:55.710 --> 00:10:57.950 understanding the 3D. structure, folding and 00:10:57.950 --> 00:11:01.190 function of complex nucleic acids. She had the 00:11:01.190 --> 00:11:03.929 exact toolkit required for the next massive leap. 00:11:04.269 --> 00:11:06.629 The transition from structural biology to genome 00:11:06.629 --> 00:11:09.009 editing, it started not with an epiphany in a 00:11:09.009 --> 00:11:11.049 dark room or a crystallography lab, but with 00:11:11.049 --> 00:11:13.389 a surprisingly modern tool. A Google search. 00:11:13.570 --> 00:11:16.490 I still love that detail. In 2006, Jillian Banfield, 00:11:16.690 --> 00:11:18.850 a Berkeley colleague studying microbial genomics, 00:11:19.009 --> 00:11:21.529 was looking for someone who understood RNA interference, 00:11:21.990 --> 00:11:24.870 RNAi, to help interpret these mysterious repeating 00:11:24.870 --> 00:11:27.669 DNA sequences she kept finding in bacteria. So 00:11:27.669 --> 00:11:31.629 she literally searched RNAi in UC Berkeley. And 00:11:31.629 --> 00:11:34.509 dude, nah. because of her extensive work on RNA 00:11:34.509 --> 00:11:36.850 structure, came up right at the top of the list. 00:11:37.029 --> 00:11:39.049 It just shows the sheer weight of Doudna's prior 00:11:39.049 --> 00:11:42.129 work. That initial contact led to Doudna investigating 00:11:42.129 --> 00:11:45.429 this unusual system, CRISPR. Right. CRISPR stands 00:11:45.429 --> 00:11:48.789 for Clustered Regularly Interspaced Short Palindromic 00:11:48.789 --> 00:11:51.649 Repeats, which is a mouthful. A total mouthful. 00:11:51.710 --> 00:11:54.029 At the time, it was just a genomic curiosity. 00:11:54.649 --> 00:11:57.690 And it was known that the sequences acted as 00:11:57.690 --> 00:12:00.929 a kind of bacterial immune system. When a bacterium 00:12:00.929 --> 00:12:03.690 survived a viral attack, it would snip a piece 00:12:03.690 --> 00:12:06.090 of the viral DNA and store it in its own genome, 00:12:06.230 --> 00:12:08.409 right between those short repeating sequences. 00:12:08.669 --> 00:12:11.450 It was like a molecular mugshot database. That's 00:12:11.450 --> 00:12:13.509 the perfect way to describe it. The system itself 00:12:13.509 --> 00:12:16.070 was first noted by Yoshizumi Ishino way back 00:12:16.070 --> 00:12:19.149 in 1987, but Francisco Mojica later characterized 00:12:19.149 --> 00:12:21.549 it, suggesting it was an immune system. They 00:12:21.549 --> 00:12:23.590 basically discovered the lockbox. But the key 00:12:23.590 --> 00:12:26.320 was missing. The key was missing. And the breakthrough 00:12:26.320 --> 00:12:28.559 that unlocked the whole thing happened in collaboration 00:12:28.559 --> 00:12:31.919 with Emmanuel Charpentier, a Swedish microbiologist 00:12:31.919 --> 00:12:34.480 dude that met at a conference in 2011. Their 00:12:34.480 --> 00:12:37.100 core realization, published in 2012, was that 00:12:37.100 --> 00:12:40.000 this microbial immunity system, which uses the 00:12:40.000 --> 00:12:42.960 Cas9 protein as a molecular scissor, could be 00:12:42.960 --> 00:12:45.539 simplified and repurposed. They showed it was 00:12:45.539 --> 00:12:48.340 a universal... programmable editing tool. Okay, 00:12:48.419 --> 00:12:50.320 let's break down the mechanics because this is 00:12:50.320 --> 00:12:53.580 the core of the invention. In nature, the Cas9 00:12:53.580 --> 00:12:56.360 protein works with two RNA molecules. There's 00:12:56.360 --> 00:12:59.279 the CarNA, the CRISPR RNA, which carries the 00:12:59.279 --> 00:13:01.720 targeting sequence matching the viral DNA. And 00:13:01.720 --> 00:13:03.960 then there's the trach RNA or transactivating 00:13:03.960 --> 00:13:06.460 CRISPR RNA, which acts as a kind of scaffold 00:13:06.460 --> 00:13:09.850 to activate the Cas9 protein. So Doudna and Charpentier's 00:13:09.850 --> 00:13:12.409 genius was simplifying this complex two -part 00:13:12.409 --> 00:13:15.990 system into one single engineered molecule, the 00:13:15.990 --> 00:13:20.049 single guide RNA, or sgRNA. Yes. This sgRNA contained 00:13:20.049 --> 00:13:22.370 both the targeting information and the scaffold 00:13:22.370 --> 00:13:25.110 necessary to recruit and activate the Cas9 enzyme. 00:13:25.690 --> 00:13:28.450 all in one piece. That simplification was revolutionary. 00:13:28.549 --> 00:13:30.570 It means if you want to cut a piece of DNA, you 00:13:30.570 --> 00:13:32.889 just synthesize an sgRNA that matches your target 00:13:32.889 --> 00:13:35.289 sequence, pair it with the Cas9 protein, and 00:13:35.289 --> 00:13:37.549 put it in the cell. The guide RNA directs the 00:13:37.549 --> 00:13:40.350 Cas9 to the precise location in the genome. And 00:13:40.350 --> 00:13:42.309 this brings us to one of the most crucial pieces 00:13:42.309 --> 00:13:44.389 of molecular detail that often gets overlooked, 00:13:44.629 --> 00:13:47.850 but is so essential for you to understand. And 00:13:47.850 --> 00:13:51.370 that's the protospacer -adjacent motif. The PAM 00:13:51.370 --> 00:13:54.529 sequence. The PAM sequence. Okay, why is that 00:13:54.529 --> 00:13:57.610 specific short sequence so important? The PAM 00:13:57.610 --> 00:14:00.029 sequence, it's usually just two to six base pairs 00:14:00.029 --> 00:14:03.029 long, and it's the molecular handshake. It's 00:14:03.029 --> 00:14:05.389 a specific sequence that must exist right next 00:14:05.389 --> 00:14:08.090 to the target site in the host DNA. And Cas9 00:14:08.090 --> 00:14:11.190 won't cut unless it sees that. Cas9 does not 00:14:11.190 --> 00:14:14.549 cut unless it first recognizes and binds to that 00:14:14.549 --> 00:14:17.269 PAM sequence. This acts as a critical safety 00:14:17.269 --> 00:14:20.549 feature for the bacteria. It ensures Cas9 only 00:14:20.549 --> 00:14:23.129 targets foreign invaders, and it prevents the 00:14:23.129 --> 00:14:25.970 system from slicing up the bacterium's own stored 00:14:25.970 --> 00:14:28.409 CRISPR sequences. Okay, so Doudna and Charpentier 00:14:28.409 --> 00:14:30.710 didn't just show that Cas9 could cut. They showed 00:14:30.710 --> 00:14:33.210 that because the guide RNA was so easily swappable, 00:14:33.370 --> 00:14:36.309 the entire system could be aimed at any desired 00:14:36.309 --> 00:14:38.850 sequence in the genome of any organism. As long 00:14:38.850 --> 00:14:40.690 as there was a PAM sequence nearby. Right. It 00:14:40.690 --> 00:14:43.629 demonstrated full programmability. Exactly. That 00:14:43.629 --> 00:14:45.730 flexibility is why it's called a revolution. 00:14:46.330 --> 00:14:49.049 You don't need years of... re -engineering specific 00:14:49.049 --> 00:14:51.809 enzymes for specific targets anymore. You just 00:14:51.809 --> 00:14:53.769 change the RNA sequence in the guide molecule. 00:14:54.370 --> 00:14:58.129 This ease, precision, and speed transformed the 00:14:58.129 --> 00:15:00.269 landscape of biological research almost overnight. 00:15:00.529 --> 00:15:02.990 The ensuing recognition was pretty much inevitable. 00:15:03.370 --> 00:15:05.870 They were jointly awarded the 2020 Nobel Prize 00:15:05.870 --> 00:15:08.409 in Chemistry for this development, solidifying 00:15:08.409 --> 00:15:10.470 its place as one of the most significant biological 00:15:10.470 --> 00:15:13.860 breakthroughs ever. A tool, this powerful one, 00:15:13.980 --> 00:15:17.419 that allows us to edit evolution itself. It naturally 00:15:17.419 --> 00:15:20.259 explodes into three distinct and very high stakes 00:15:20.259 --> 00:15:23.559 theaters. Immense applications, necessary ethical 00:15:23.559 --> 00:15:27.159 debates, and brutal intellectual property battles. 00:15:27.399 --> 00:15:29.159 Yeah, that's a good way to put it. Let's start 00:15:29.159 --> 00:15:31.899 with the incredible potential. The applications 00:15:31.899 --> 00:15:34.320 are immediate and profound. They touch everything 00:15:34.320 --> 00:15:36.700 from fundamental research to global food security. 00:15:37.000 --> 00:15:39.059 Beyond just understanding basic cell function, 00:15:39.360 --> 00:15:41.720 which has already accelerated so rapidly, we 00:15:41.720 --> 00:15:44.179 see immediate therapeutic promise. Our sources 00:15:44.179 --> 00:15:46.379 list treatments for severe inherited conditions 00:15:46.379 --> 00:15:50.240 like sickle cell anemia, cystic fibrosis, Huntington's 00:15:50.240 --> 00:15:53.200 disease. The precision allows scientists to correct 00:15:53.200 --> 00:15:56.059 the single faulty gene responsible for the condition. 00:15:56.360 --> 00:15:58.940 It's incredible. And it's not just genetic disorders. 00:15:59.220 --> 00:16:02.649 I mean, consider HIV. The virus integrates its 00:16:02.649 --> 00:16:06.179 DNA into the host cell's genome. CRISPR offers 00:16:06.179 --> 00:16:09.419 the possibility of precisely excising that viral 00:16:09.419 --> 00:16:12.600 DNA from T cells, effectively curing a persistent 00:16:12.600 --> 00:16:15.460 infection that conventional drugs can only manage. 00:16:15.659 --> 00:16:17.539 And then there's the massive applications in 00:16:17.539 --> 00:16:20.019 plant and animal research, dramatically shortening 00:16:20.019 --> 00:16:22.120 the time needed to develop sustainable, disease 00:16:22.120 --> 00:16:25.120 -resistant crops. But the magnitude of this power 00:16:25.120 --> 00:16:28.039 demanded an immediate and careful ethical framework. 00:16:28.320 --> 00:16:30.580 And Doudna was one of the first scientists to 00:16:30.580 --> 00:16:32.740 really sound the alarm on the technology she 00:16:32.740 --> 00:16:34.879 helped create. Her role as a thought leader here 00:16:34.879 --> 00:16:37.639 is just crucial. Recognizing how fast the field 00:16:37.639 --> 00:16:39.580 was moving, Doudna, along with other leading 00:16:39.580 --> 00:16:42.220 biologists, called for an immediate worldwide 00:16:42.220 --> 00:16:44.940 moratorium on certain clinical applications of 00:16:44.940 --> 00:16:47.480 gene editing. Very early on, she helped force 00:16:47.480 --> 00:16:49.799 the global community to pause and consider the 00:16:49.799 --> 00:16:52.460 implications. The key ethical distinction here, 00:16:52.539 --> 00:16:54.320 which is essential for our listeners to grasp, 00:16:54.519 --> 00:16:56.820 is the difference between somatic and germline 00:16:56.820 --> 00:16:59.820 editing. How does Doudna draw that line? She 00:16:59.820 --> 00:17:02.759 strongly supports somatic gene editing. Soma 00:17:02.759 --> 00:17:07.019 means body. These are changes made to non -reproductive 00:17:07.019 --> 00:17:09.559 body cells, like liver cells or blood cells. 00:17:10.019 --> 00:17:12.359 These edits are confined to the individual patient, 00:17:12.519 --> 00:17:14.940 they treat the disease, and they do not get passed 00:17:14.940 --> 00:17:17.059 down to the next generation. This is essentially 00:17:17.059 --> 00:17:19.160 just treating the individual with a highly advanced 00:17:19.160 --> 00:17:21.859 form of medicine. But she opposes germline gene 00:17:21.859 --> 00:17:25.019 editing. Yes. Germline editing involves making 00:17:25.019 --> 00:17:28.380 changes to embryos, eggs, or sperm, the reproductive 00:17:28.380 --> 00:17:31.160 cells. Any edit made here is inheritable. It 00:17:31.160 --> 00:17:33.000 gets passed down to all future generations. And 00:17:33.000 --> 00:17:34.799 this is where the scientific community's deepest 00:17:34.799 --> 00:17:37.980 ethical concerns lie. It is. You're moving beyond 00:17:37.980 --> 00:17:40.819 therapy for an individual to potentially altering 00:17:40.819 --> 00:17:44.259 the human gene pool forever. Dedna has been really 00:17:44.259 --> 00:17:46.500 emphatic in her opposition to germline editing, 00:17:46.660 --> 00:17:49.180 especially for non -therapeutic enhancement purposes. 00:17:49.480 --> 00:17:51.740 It shows a scientist fully aware that she has 00:17:51.740 --> 00:17:54.559 created a tool that, in her words, holds the 00:17:54.559 --> 00:17:58.130 unthinkable power to control evolution. And that 00:17:58.130 --> 00:18:00.650 awareness is why she stepped into the ethical 00:18:00.650 --> 00:18:03.349 arena, understanding that the science was just 00:18:03.349 --> 00:18:06.690 moving faster than the societal consensus. Now, 00:18:06.789 --> 00:18:09.609 in parallel with this ethical debate, the question 00:18:09.609 --> 00:18:12.690 of who owned this foundational technology, it 00:18:12.690 --> 00:18:15.230 became a legal cage match. It really did. Yeah. 00:18:15.289 --> 00:18:17.630 The high stakes intellectual property conflict 00:18:17.630 --> 00:18:21.710 that defined the mid 2010s. This was the complex 00:18:21.710 --> 00:18:24.509 patent war between the UC Berkeley team, led 00:18:24.509 --> 00:18:27.069 by Doudna and Charpentier, and the Broad Institute 00:18:27.069 --> 00:18:30.329 of MIT and Harvard, primarily featuring Feng 00:18:30.329 --> 00:18:32.789 Zhang. The stakes were astronomical. We're talking 00:18:32.789 --> 00:18:35.589 potentially trillions of dollars in future royalties. 00:18:35.809 --> 00:18:37.789 So what was the core difference in their patent 00:18:37.789 --> 00:18:40.329 claims? The conflict revolved around the timeline 00:18:40.329 --> 00:18:43.170 and the context of application. The Doudnaw UC 00:18:43.170 --> 00:18:45.569 Berkeley team's claim was based on the fundamental 00:18:45.569 --> 00:18:48.730 description or conception of the universal programmable 00:18:48.730 --> 00:18:52.049 system. So they showed how to engineer the sgRNA 00:18:52.049 --> 00:18:54.990 to cut any DNA in a test tube, and they detailed 00:18:54.990 --> 00:18:56.670 the theory of how it would work in more complex 00:18:56.670 --> 00:18:58.609 cells. Right. And the Broad Institute's argument? 00:18:58.960 --> 00:19:01.519 The Broad Institute, a few months later, demonstrated 00:19:01.519 --> 00:19:04.099 that the Cas9 system could successfully edit 00:19:04.099 --> 00:19:08.240 genes specifically in eukaryotic cells, complex 00:19:08.240 --> 00:19:11.019 cells, like human cells, that contain a nucleus. 00:19:11.359 --> 00:19:14.440 So their legal argument centered on reduction 00:19:14.440 --> 00:19:17.359 to practice. Exactly. That they were the first 00:19:17.359 --> 00:19:20.160 to provide physical, published evidence that 00:19:20.160 --> 00:19:21.839 the system worked in the complex environment 00:19:21.839 --> 00:19:24.339 of human cells, which was an environment that 00:19:24.339 --> 00:19:26.059 had been considered much harder to penetrate. 00:19:26.460 --> 00:19:29.319 So the argument boiled down to... Who should 00:19:29.319 --> 00:19:31.940 get the patent? The inventor who conceived of 00:19:31.940 --> 00:19:33.960 the fundamental tool and explained how it could 00:19:33.960 --> 00:19:36.519 be used universally. Or the team that first provided 00:19:36.519 --> 00:19:38.720 empirical proof that it worked in the most economically 00:19:38.720 --> 00:19:42.240 valuable cells, namely human cells. That's the 00:19:42.240 --> 00:19:45.579 core legal and philosophical divide. In 2017, 00:19:45.940 --> 00:19:48.220 the U .S. Patent Trial and Appeal Board initially 00:19:48.220 --> 00:19:50.799 favored the Broad Institute regarding the specific 00:19:50.799 --> 00:19:53.700 claims involving application in eukaryotic cells. 00:19:54.059 --> 00:19:56.359 It was a complex ruling because it suggested 00:19:56.359 --> 00:19:58.859 that applying a known system to a new environment 00:19:58.859 --> 00:20:01.700 could be considered a non -obvious patentable 00:20:01.700 --> 00:20:04.299 invention, separate from the original invention 00:20:04.299 --> 00:20:06.059 of the system itself. But that wasn't the final 00:20:06.059 --> 00:20:09.960 word, was it? No, far from it. The UC Berkeley 00:20:09.960 --> 00:20:12.519 group eventually received broader patents covering 00:20:12.519 --> 00:20:14.980 the general technique of programmable gene editing. 00:20:15.259 --> 00:20:18.579 And on top of that, the European landscape offered 00:20:18.579 --> 00:20:20.839 a completely different result. What happened 00:20:20.839 --> 00:20:23.900 in Europe? The European Patent Office disallowed 00:20:23.900 --> 00:20:26.900 the broad institute's initial claim due to a 00:20:26.900 --> 00:20:30.279 procedural flaw. It was related to who was listed 00:20:30.279 --> 00:20:32.539 on the patent application versus the original 00:20:32.539 --> 00:20:35.000 scientific publication. A legal technicality. 00:20:35.039 --> 00:20:37.400 A very important one. It shifted the momentum 00:20:37.400 --> 00:20:40.339 significantly. suggesting the UC Berkeley group 00:20:40.339 --> 00:20:42.400 would likely hold stronger patent positions in 00:20:42.400 --> 00:20:45.019 Europe for the general method. The whole patent 00:20:45.019 --> 00:20:47.980 landscape is still this multifaceted, high -value 00:20:47.980 --> 00:20:50.539 conflict. Despite that intense rivalry, which 00:20:50.539 --> 00:20:52.539 Dodna described at one point as feeling like 00:20:52.539 --> 00:20:55.420 a divorce, this period fueled immediate commercial 00:20:55.420 --> 00:20:57.640 efforts. Yeah, she jumped into entrepreneurship 00:20:57.640 --> 00:21:00.259 almost instantly to translate the technology 00:21:00.259 --> 00:21:03.299 into usable treatments and diagnostics. She recognized 00:21:03.299 --> 00:21:05.599 that foundational research, no matter how profound, 00:21:05.819 --> 00:21:08.599 needs a mechanism to reach patients. She co -founded 00:21:08.599 --> 00:21:11.220 Caribou Biosciences in 2011, even before the 00:21:11.220 --> 00:21:13.599 seminal paper was published. And she was briefly 00:21:13.599 --> 00:21:16.180 involved in Editus Medicine, which also focused 00:21:16.180 --> 00:21:18.839 on gene therapy. Briefly. She was a co -founder 00:21:18.839 --> 00:21:22.480 in September 2013 alongside Zhang, but she resigned 00:21:22.480 --> 00:21:25.859 in June 2014, reflecting the complexity and strain 00:21:25.859 --> 00:21:28.500 of that early competitive environment. But she 00:21:28.500 --> 00:21:31.589 shifted her focus. co -founding Intelia Therapeutics, 00:21:31.730 --> 00:21:34.509 which is explicitly focused on in vivo gene editing, 00:21:34.710 --> 00:21:37.369 delivering the CRISPR tools directly into the 00:21:37.369 --> 00:21:39.589 patient's body to treat genetic diseases. And 00:21:39.589 --> 00:21:42.430 critically, she later co -founded Scribe Therapeutics. 00:21:42.569 --> 00:21:45.250 They're focused on next generation CRISPR tools, 00:21:45.569 --> 00:21:49.869 specifically Scribe pioneered CasX, a newly discovered 00:21:49.869 --> 00:21:53.210 family of Cas proteins. Why are these next generation 00:21:53.210 --> 00:21:55.730 Cas proteins so important? I mean, isn't Cas9 00:21:55.730 --> 00:21:58.609 the gold standard? Cas9 is a very large protein, 00:21:58.690 --> 00:22:00.440 which makes... it challenging to package into 00:22:00.440 --> 00:22:02.500 delivery vehicles, like the viruses that are 00:22:02.500 --> 00:22:04.960 used to shuttle the gene editor into human cells. 00:22:05.599 --> 00:22:08.180 CasX, which Scribe focuses on, is significantly 00:22:08.180 --> 00:22:11.059 more compact. Its smaller size means it can be 00:22:11.059 --> 00:22:13.259 delivered more easily and efficiently, opening 00:22:13.259 --> 00:22:15.500 up new avenues for treatment where size constraints 00:22:15.500 --> 00:22:17.660 were a major hurdle. So she's not just focused 00:22:17.660 --> 00:22:20.579 on application, but on constantly improving the 00:22:20.579 --> 00:22:23.339 tool itself. Right. Her entrepreneurial endeavors 00:22:23.339 --> 00:22:25.700 really demonstrate that the goal isn't just winning 00:22:25.700 --> 00:22:28.559 a Nobel Prize. It's ensuring the mechanism gets 00:22:28.559 --> 00:22:31.420 out into the world to solve real problems. You 00:22:31.420 --> 00:22:33.460 know, for most scientists, the Nobel Prize is 00:22:33.460 --> 00:22:37.240 the culmination of a career. But for Doudna, 00:22:37.259 --> 00:22:38.859 it seems to have been more of a launching pad. 00:22:39.019 --> 00:22:41.599 A launching pad for massive institution -building 00:22:41.599 --> 00:22:44.900 work focused on societal impact. And her primary 00:22:44.900 --> 00:22:47.799 vehicle for this is the Innovative Genomics Institute, 00:22:48.059 --> 00:22:52.059 or IGI. She co -founded it in 2014 and serves 00:22:52.059 --> 00:22:54.779 as its director. leveraging this collaboration 00:22:54.779 --> 00:22:58.079 between UC Berkeley and UCSF. The IGI's mandate 00:22:58.079 --> 00:23:00.859 is huge. It's designed to accelerate the application 00:23:00.859 --> 00:23:03.480 of genome editing technology to three pillars 00:23:03.480 --> 00:23:06.640 of major societal problems, human health, sustainable 00:23:06.640 --> 00:23:09.640 agriculture, and climate change. That goes far 00:23:09.640 --> 00:23:12.599 beyond basic lab science. It does. So what does 00:23:12.599 --> 00:23:14.339 that kind of ambitious research look like on 00:23:14.339 --> 00:23:16.680 a day -to -day level in her lab today? Well, 00:23:16.720 --> 00:23:18.779 they maintain a focus on optimizing the tool. 00:23:19.500 --> 00:23:21.720 They continue to study the structure and function 00:23:21.720 --> 00:23:24.799 of diverse CRISPR -Cas systems, like CasX and 00:23:24.799 --> 00:23:28.140 Cas12, always looking for a better, more precise 00:23:28.140 --> 00:23:30.859 molecular cutter. But the applied work is massive. 00:23:31.019 --> 00:23:33.380 Oh, yeah. They're dedicating significant resources 00:23:33.380 --> 00:23:35.839 to developing novel and efficient delivery mechanisms, 00:23:36.079 --> 00:23:39.240 just figuring out how to safely and precisely 00:23:39.240 --> 00:23:42.680 target the molecular scissors to the right cells 00:23:42.680 --> 00:23:44.279 in the body. And you mentioned a fascinating 00:23:44.279 --> 00:23:47.390 novel technique they're researching. Precisely 00:23:47.390 --> 00:23:50.250 editing microbiomes. That seems incredibly complex. 00:23:50.630 --> 00:23:53.690 It is, but the potential is enormous. Instead 00:23:53.690 --> 00:23:56.430 of editing human cells, they're developing ways 00:23:56.430 --> 00:24:00.069 to use CRISPR to precisely edit the complex microbial 00:24:00.069 --> 00:24:02.450 communities that inhabit our bodies or our soil. 00:24:02.650 --> 00:24:04.890 So you could, what, eradicate antibiotic -resistant 00:24:04.890 --> 00:24:07.289 bacteria? Potentially. Or you could engineer 00:24:07.289 --> 00:24:10.009 soil microbiomes to sequester carbon more effectively, 00:24:10.269 --> 00:24:12.529 directly addressing climate change and human 00:24:12.529 --> 00:24:14.940 health challenges at the same time. That focus 00:24:14.940 --> 00:24:17.859 on immediate large -scale application was starkly 00:24:17.859 --> 00:24:20.240 illustrated by her response to the global COVID 00:24:20.240 --> 00:24:23.599 -19 crisis. Absolutely. The pandemic hit in early 00:24:23.599 --> 00:24:26.980 2020, and Doudna immediately mobilized the IGI 00:24:26.980 --> 00:24:29.750 infrastructure. She quickly organized an effort 00:24:29.750 --> 00:24:32.890 to repurpose CRISPR -based technologies to address 00:24:32.890 --> 00:24:35.089 the virus. They didn't just study it. They acted 00:24:35.089 --> 00:24:38.309 as a public health service. The IGI testing center 00:24:38.309 --> 00:24:40.829 ended up processing a massive volume over half 00:24:40.829 --> 00:24:43.190 a million patient samples. Right from the youthy 00:24:43.190 --> 00:24:45.490 community and surrounding critical areas, including 00:24:45.490 --> 00:24:47.470 essential farm workers in the Salinas Valley. 00:24:47.849 --> 00:24:50.170 It really proved the power of having such a dynamic 00:24:50.170 --> 00:24:52.990 research infrastructure ready to pivot. And on 00:24:52.990 --> 00:24:55.829 top of that, her diagnostics company, Mammoth 00:24:55.829 --> 00:24:59.430 Biosciences, played a key role. Yes, in developing 00:24:59.430 --> 00:25:02.130 a rapid, CRISPR -based point -of -need diagnostic 00:25:02.130 --> 00:25:05.279 test for COVID -19. This diagnostic test was 00:25:05.279 --> 00:25:07.519 noted as being much faster and less expensive 00:25:07.519 --> 00:25:10.579 than the traditional QRT -PCR tests that were 00:25:10.579 --> 00:25:12.819 being used widely at the time. It showed that 00:25:12.819 --> 00:25:15.700 CRISPR isn't just about editing genes. It's also 00:25:15.700 --> 00:25:18.640 a highly sensitive biosensing tool. And that's 00:25:18.640 --> 00:25:21.319 what Mammoth Biosciences focuses on. Exactly. 00:25:21.319 --> 00:25:24.519 She co -founded it in 2017. And it focuses entirely 00:25:24.519 --> 00:25:28.140 on leveraging this sensing capability of CRISPR 00:25:28.140 --> 00:25:30.940 to create rapid, precise diagnostic tests across 00:25:30.940 --> 00:25:34.400 various fields. Healthcare, agriculture. biodefense, 00:25:34.400 --> 00:25:36.880 environmental monitoring. So it's a crucial commercial 00:25:36.880 --> 00:25:39.500 strategy, using the precision of Cas proteins 00:25:39.500 --> 00:25:42.740 for rapid detection, not just for cutting. Right. 00:25:42.880 --> 00:25:45.940 And beyond her direct work, her influence spans 00:25:45.940 --> 00:25:48.460 the entire scientific and financial landscape. 00:25:48.700 --> 00:25:51.740 She holds major advisory roles, guiding investment 00:25:51.740 --> 00:25:54.559 decisions for colossal entities like Altos Labs, 00:25:54.920 --> 00:25:56.839 Johnson & Johnson, and Sixth Street Partners. 00:25:57.289 --> 00:25:59.430 That kind of institutional weight shows that 00:25:59.430 --> 00:26:01.670 the decisions she makes ripple across global 00:26:01.670 --> 00:26:04.549 capital investment in biotech. And here is a 00:26:04.549 --> 00:26:06.769 striking testament to her stature in computational 00:26:06.769 --> 00:26:09.490 science, even though she is fundamentally a biochemist. 00:26:09.529 --> 00:26:11.970 The announcement in 2025 that a new supercomputer 00:26:11.970 --> 00:26:14.609 was being named after her. The Doudna supercomputer. 00:26:15.359 --> 00:26:17.420 Intended for the National Energy Research Scientific 00:26:17.420 --> 00:26:19.880 Computing Center at LBNL, it's going to be the 00:26:19.880 --> 00:26:22.259 successor to the Perlmutter supercomputer, focusing 00:26:22.259 --> 00:26:24.960 on integrating AI into massive scientific research 00:26:24.960 --> 00:26:28.380 calculations. To have a major piece of national 00:26:28.380 --> 00:26:31.140 computational infrastructure, named after you, 00:26:31.240 --> 00:26:33.740 shows an influence that just transcends your 00:26:33.740 --> 00:26:36.630 original discipline. It acknowledges the computational 00:26:36.630 --> 00:26:39.089 revolution that CRISPR started. And to ground 00:26:39.089 --> 00:26:41.750 this monumental figure, we can look at some of 00:26:41.750 --> 00:26:44.150 the personal details that humanize her ambition. 00:26:44.529 --> 00:26:47.309 She's married to Jamie Cate, who is also a distinguished 00:26:47.309 --> 00:26:50.130 professor at Berkeley. And his own work intersects 00:26:50.130 --> 00:26:52.750 perfectly with the IGI's mission. He focuses 00:26:52.750 --> 00:26:56.109 on using gene -editing yeast for biofuel production. 00:26:56.349 --> 00:26:59.299 It's a family dedicated to applied science. The 00:26:59.299 --> 00:27:01.460 source material even notes their move to Berkeley 00:27:01.460 --> 00:27:04.039 in 2002 was partially because Kate preferred 00:27:04.039 --> 00:27:06.099 the less formal, research -focused environment 00:27:06.099 --> 00:27:08.000 of the West Coast. And, you know, continuing 00:27:08.000 --> 00:27:10.180 the tradition of curiosity and technological 00:27:10.180 --> 00:27:13.940 focus, their son, born in 2002, is currently 00:27:13.940 --> 00:27:16.700 attending UC Berkeley. Studying electrical engineering 00:27:16.700 --> 00:27:19.000 and computer science. It's a powerful legacy 00:27:19.000 --> 00:27:21.839 of foundational and applied science. So we've 00:27:21.839 --> 00:27:24.039 navigated the full scope of Jennifer Downer's 00:27:24.039 --> 00:27:26.829 career. The key takeaway for you, the listener, 00:27:26.970 --> 00:27:29.369 is really understanding that the greatest applied 00:27:29.369 --> 00:27:32.369 breakthroughs often spring from the most detailed, 00:27:32.589 --> 00:27:37.069 basic, and seemingly obscure fundamental research. 00:27:37.329 --> 00:27:40.789 Right, the structural knowledge she gained. Bainstakingly 00:27:40.789 --> 00:27:43.589 solving the 3D architecture of ribozymes and 00:27:43.589 --> 00:27:46.130 realizing that RNA could fold into these complex 00:27:46.130 --> 00:27:48.670 functional shapes using elements like clustered 00:27:48.670 --> 00:27:51.130 magnesium ions, that was the crucial foundation. 00:27:51.529 --> 00:27:53.869 It was everything. Without that deep expertise 00:27:53.869 --> 00:27:56.690 in nucleic acid structure, the breakthrough of 00:27:56.690 --> 00:27:59.910 engineering the single guide RNA to program Cas9 00:27:59.910 --> 00:28:02.450 simply couldn't have happened. Her journey really 00:28:02.450 --> 00:28:05.349 confirms that basic curiosity fueled by books 00:28:05.349 --> 00:28:07.950 like The Double Helix ultimately culminated in 00:28:07.950 --> 00:28:10.279 the creation of this universe. tool. A tool that 00:28:10.279 --> 00:28:12.359 addresses humanity's most persistent challenges, 00:28:12.420 --> 00:28:15.279 from inherited disease correction to developing 00:28:15.279 --> 00:28:17.940 climate resilient agriculture. And as she co 00:28:17.940 --> 00:28:20.539 -authored in her book, A Crack in Creation, the 00:28:20.539 --> 00:28:23.500 power she helped unleash truly is an unthinkable 00:28:23.500 --> 00:28:26.839 power. She remains focused, not so much on the 00:28:26.839 --> 00:28:29.359 science now, the science is largely solved, but 00:28:29.359 --> 00:28:32.240 on the sociological challenge of access and equity. 00:28:32.829 --> 00:28:35.390 She has stated very clearly that she is, and 00:28:35.390 --> 00:28:37.529 I'm quoting here, concerned that the benefits 00:28:37.529 --> 00:28:40.069 of the technology might not reach those who need 00:28:40.069 --> 00:28:42.390 it most if we're not thoughtful and deliberate 00:28:42.390 --> 00:28:45.269 about how we develop the technology. So the challenge 00:28:45.269 --> 00:28:48.089 has shifted from making the tool work to ensuring 00:28:48.089 --> 00:28:50.930 the tool benefits all of humanity, not just privileged 00:28:50.930 --> 00:28:53.529 segments. Exactly. So we leave you with this 00:28:53.529 --> 00:28:57.039 final provocative question to consider. If CRISPR 00:28:57.039 --> 00:28:59.420 technology allows us to fundamentally solve issues 00:28:59.420 --> 00:29:02.140 in health, agriculture and climate change simultaneously, 00:29:02.619 --> 00:29:05.420 and this technology is largely owned and commercialized 00:29:05.420 --> 00:29:08.200 by private companies, whose responsibility is 00:29:08.200 --> 00:29:10.680 it? The scientist who creates the tool, the government 00:29:10.680 --> 00:29:12.880 that regulates it or the market that commercializes 00:29:12.880 --> 00:29:16.420 it to actively ensure the benefits of this unthinkable 00:29:16.420 --> 00:29:19.420 power are distributed equitably across the globe. 00:29:19.579 --> 00:29:21.920 Something to reflect upon as we witness the code 00:29:21.920 --> 00:29:24.359 of life continuing to be rewritten. Thanks for 00:29:24.359 --> 00:29:26.259 diving deep with us. We'll see you next time.