WEBVTT 00:00:00.000 --> 00:00:01.760 Welcome back to The Deep Dive. Today we've got 00:00:01.760 --> 00:00:04.320 a story that, honestly, it feels like one of 00:00:04.320 --> 00:00:06.339 those movie scripts you'd reject because it's 00:00:06.339 --> 00:00:08.439 just a little too unbelievable. It really does. 00:00:08.539 --> 00:00:10.560 It has all the elements, right? You've got extreme 00:00:10.560 --> 00:00:14.460 poverty, a hero who basically has to teach herself 00:00:14.460 --> 00:00:17.079 everything. Then you have the entire scientific 00:00:17.079 --> 00:00:19.519 establishment, I mean everyone, saying, you're 00:00:19.519 --> 00:00:23.160 crazy, this will never work. And then, after 00:00:23.160 --> 00:00:26.320 all that, a discovery they want to talk to it. 00:00:27.120 --> 00:00:29.480 It just fundamentally changes how we understand 00:00:29.480 --> 00:00:31.940 life itself. And we're not being metaphorical. 00:00:31.940 --> 00:00:33.820 We aren't talking about the meaning of life. 00:00:33.859 --> 00:00:36.679 We're talking about the actual physical machinery. 00:00:36.939 --> 00:00:39.320 Nuts and bolts. The factory floor of biology, 00:00:39.600 --> 00:00:42.240 really. We're talking about the ribosome and 00:00:42.240 --> 00:00:45.240 the woman who finally cracked its code, Ada Yonath. 00:00:46.660 --> 00:00:49.100 Now, before we get into the, you know, the really 00:00:49.100 --> 00:00:51.359 heavy science and we will get into it because 00:00:51.359 --> 00:00:53.979 you can't appreciate the victory without understanding 00:00:53.979 --> 00:00:56.840 the fight. That's true. We need to set the stage 00:00:56.840 --> 00:00:59.159 for the sheer magnitude of this thing. OK, think 00:00:59.159 --> 00:01:02.140 of it like this. For decades, we knew DNA was 00:01:02.140 --> 00:01:04.299 the blueprint. The instructions. The instructions. 00:01:04.379 --> 00:01:06.439 Exactly. We knew they were in there, but we didn't 00:01:06.439 --> 00:01:07.840 really have a clue how the cell actually took 00:01:07.840 --> 00:01:09.780 those instructions and, you know, built a living 00:01:09.780 --> 00:01:13.140 thing from them. The machine doing the work, 00:01:13.180 --> 00:01:16.299 the rhizome, was just a total black box. A black 00:01:16.299 --> 00:01:18.900 box that almost everyone in the field was convinced 00:01:18.900 --> 00:01:22.319 was impossible to open. That is the key. Impossible. 00:01:23.120 --> 00:01:25.019 Formidable. That was the word they always used. 00:01:25.219 --> 00:01:28.140 Formidable challenges. Which, you know, is just 00:01:28.140 --> 00:01:30.680 the polite academic way of saying, don't even 00:01:30.680 --> 00:01:33.599 bother, you are going to fail. But Edie Yonath 00:01:33.599 --> 00:01:36.319 didn't listen. Thankfully. And because she didn't 00:01:36.319 --> 00:01:38.560 listen... We now have a completely different, 00:01:38.640 --> 00:01:41.439 a radically different understanding of how antibiotics 00:01:41.439 --> 00:01:45.060 work, how drug resistance happens, and even the 00:01:45.060 --> 00:01:47.200 very history of life on Earth. And the incredible 00:01:47.200 --> 00:01:49.620 part is she did all of it, starting from a place 00:01:49.620 --> 00:01:51.480 where she literally didn't even have money for 00:01:51.480 --> 00:01:53.560 a notebook. Let's start right there. Let's go 00:01:53.560 --> 00:01:56.459 back to 1939, the guerrilla quarter of Jerusalem. 00:01:56.859 --> 00:01:59.599 Can you sort of paint a picture for us? So, yeah, 00:01:59.659 --> 00:02:03.120 1939. This is pre -state Israel, so it's the 00:02:03.120 --> 00:02:05.900 British Mandate of Palestine. And it's a time 00:02:05.900 --> 00:02:09.960 of just incredible tension of uncertainty. And 00:02:09.960 --> 00:02:13.439 for Ada's family, the Lifshitz family, that was 00:02:13.439 --> 00:02:16.199 her maiden name, it was a time of just grinding 00:02:16.199 --> 00:02:19.659 poverty. Her parents, Hillel and Esther, they 00:02:19.659 --> 00:02:21.280 were from Poland, right? That's right. They were 00:02:21.280 --> 00:02:23.580 Zionist Jews, and they had immigrated from a 00:02:23.580 --> 00:02:27.240 town called Zduska Wola in 1933. So they got 00:02:27.240 --> 00:02:29.939 out just in the nick of time, just before Europe 00:02:29.939 --> 00:02:32.900 really ignited. They got out. Yes. But life in 00:02:32.900 --> 00:02:35.360 Jerusalem was not the promised land they might 00:02:35.360 --> 00:02:37.919 have hoped for. Her father, he wasn't a scientist 00:02:37.919 --> 00:02:39.840 or a professor. He actually came from a long 00:02:39.840 --> 00:02:41.860 line of rabbis. But in Jerusalem, he was running 00:02:41.860 --> 00:02:44.180 a small grocery store. And when we say grocery 00:02:44.180 --> 00:02:46.389 store, we shouldn't be picturing. Like a modern 00:02:46.389 --> 00:02:49.090 supermarket? No, not at all. This was a daily 00:02:49.090 --> 00:02:51.409 struggle for survival. The source material we 00:02:51.409 --> 00:02:53.550 have is very blunt about it. It just says they 00:02:53.550 --> 00:02:55.669 found it difficult to make ends meet. And I was 00:02:55.669 --> 00:02:57.949 really struck by the description of their apartment. 00:02:58.169 --> 00:02:59.889 It wasn't just a small apartment. It was, what, 00:02:59.969 --> 00:03:02.030 a few rooms that they shared with several other 00:03:02.030 --> 00:03:04.449 families? That was very common for the time and, 00:03:04.490 --> 00:03:06.949 you know, for their economic situation. But you 00:03:06.949 --> 00:03:08.650 have to think about what that does to a child. 00:03:09.289 --> 00:03:12.449 Imagine the constant noise. Yeah. The absolute 00:03:12.449 --> 00:03:16.270 lack of privacy. No space of your... None. You 00:03:16.270 --> 00:03:18.490 are literally living on top of other people. 00:03:18.610 --> 00:03:20.669 There's no yard to run around in. There's no 00:03:20.669 --> 00:03:25.349 room for toys. And yet somehow out of that cramped, 00:03:25.409 --> 00:03:28.889 loud environment, she develops this incredibly 00:03:28.889 --> 00:03:32.370 rich internal life. There's a note here where 00:03:32.370 --> 00:03:35.110 she recalls that books were the only thing she 00:03:35.110 --> 00:03:37.789 had to keep her occupied. That's the escape hatch, 00:03:37.889 --> 00:03:40.330 isn't it? When your physical world is that constricted, 00:03:40.330 --> 00:03:42.810 you expand the mental one. Books became her whole 00:03:42.810 --> 00:03:45.610 world. And, I mean, it also says something about 00:03:45.610 --> 00:03:47.889 her parents. How so? Well, they're struggling 00:03:47.889 --> 00:03:50.090 just to put bread on the table, but they clearly 00:03:50.090 --> 00:03:52.590 valued her mind. They knew she was bright. They 00:03:52.590 --> 00:03:55.069 made sure she went to a good school in Bate -Hackram. 00:03:55.229 --> 00:03:58.310 They did, and that's such a crucial detail, because 00:03:58.310 --> 00:04:00.889 Bate -Hackram was an upscale neighborhood. It 00:04:00.889 --> 00:04:03.310 was nowhere near where they lived. They couldn't 00:04:03.310 --> 00:04:05.409 really afford it, but they were determined to 00:04:05.409 --> 00:04:07.990 give her a proper... education it's that classic 00:04:07.990 --> 00:04:10.669 immigrant story you know sacrifice everything 00:04:10.669 --> 00:04:14.050 so the kids can have a better life but then just 00:04:14.050 --> 00:04:16.230 as she's getting started the floor just drops 00:04:16.230 --> 00:04:19.129 out from under them her father dies he was only 00:04:19.129 --> 00:04:23.509 42 Ada was still a young girl just 11 and suddenly 00:04:23.509 --> 00:04:26.129 that struggling grocery store which was barely 00:04:26.129 --> 00:04:29.370 keeping them afloat It's not even an option anymore. 00:04:29.550 --> 00:04:31.949 The family just collapses financially. Completely. 00:04:32.110 --> 00:04:34.949 They have to pack up and move to Tel Aviv just 00:04:34.949 --> 00:04:37.329 to try and find some way for her mother to support 00:04:37.329 --> 00:04:39.529 them. This is the part of the story where, for 00:04:39.529 --> 00:04:42.029 most people, the academic dream would just die. 00:04:42.569 --> 00:04:44.670 You lose the main breadwinner. You're in poverty. 00:04:44.769 --> 00:04:47.209 You move to a new city. You go find a job, right? 00:04:47.230 --> 00:04:49.170 It is. You don't aim for a prestigious high school. 00:04:49.519 --> 00:04:51.459 You certainly don't aim for a place like Tikshon 00:04:51.459 --> 00:04:53.660 Hadash. That was a top tier high school. But 00:04:53.660 --> 00:04:55.899 Ada had applied and she'd been accepted. The 00:04:55.899 --> 00:04:57.939 problem obviously was the tuition. There was 00:04:57.939 --> 00:05:00.399 just no way her mother could pay it. So you have 00:05:00.399 --> 00:05:03.439 this brilliant teenager. She's grieving her father 00:05:03.439 --> 00:05:05.660 and she's holding an acceptance letter that's 00:05:05.660 --> 00:05:07.759 basically worthless. But she doesn't give up. 00:05:07.819 --> 00:05:09.600 And this is really the first time we see that, 00:05:09.639 --> 00:05:12.420 that stubbornness, that sheer force of will that's 00:05:12.420 --> 00:05:15.019 going to win her a Nobel Prize 50 years down 00:05:15.019 --> 00:05:17.300 the line. What does she do? She goes to the school. 00:05:18.129 --> 00:05:22.310 As a teenager. And she strikes a deal with them. 00:05:22.389 --> 00:05:24.689 She tells them, look, I'll give math lessons 00:05:24.689 --> 00:05:26.629 to the other students if you'll let me study 00:05:26.629 --> 00:05:29.810 here. She offers to pay her tuition that way. 00:05:29.949 --> 00:05:32.209 I just love that image. She's sitting in class 00:05:32.209 --> 00:05:34.730 next to kids whose parents can just write a check 00:05:34.730 --> 00:05:37.310 without a second thought. And she's there because 00:05:37.310 --> 00:05:39.610 she's going to be tutoring those same kids after 00:05:39.610 --> 00:05:42.029 the final bell rings. She's literally paying 00:05:42.029 --> 00:05:44.149 for her seat at the table with her own brain 00:05:44.149 --> 00:05:46.490 power. It sets a pattern for her whole life, 00:05:46.610 --> 00:05:49.310 doesn't it? It absolutely does. She learns right 00:05:49.310 --> 00:05:51.350 from the start that she has to work twice as 00:05:51.350 --> 00:05:53.750 hard as everyone else just to stay in the room. 00:05:54.649 --> 00:05:56.930 And she learns that her intellect is her primary 00:05:56.930 --> 00:05:59.769 tool for survival. And speaking of her intellect, 00:05:59.889 --> 00:06:02.170 it's around this time she reads a biography that 00:06:02.170 --> 00:06:05.009 makes a huge impression on her. Marie Curie. 00:06:05.110 --> 00:06:07.269 The famous Polish scientist. It makes perfect 00:06:07.269 --> 00:06:10.019 sense, right? Here's another woman from Poland 00:06:10.019 --> 00:06:12.720 from, you know, difficult circumstances who reaches 00:06:12.720 --> 00:06:15.459 the absolute pinnacle of science. It must have 00:06:15.459 --> 00:06:17.740 been so inspiring. But there's a really interesting 00:06:17.740 --> 00:06:20.500 nuance here. Usually when a scientist brings 00:06:20.500 --> 00:06:24.699 up Marie Curie, it's pure hero worship. She was 00:06:24.699 --> 00:06:28.000 my idol. I wanted to be just like her. But Yonath 00:06:28.000 --> 00:06:30.040 is very specific about this. She says Curie was 00:06:30.040 --> 00:06:33.240 an inspiration, but not a role model. It's such 00:06:33.240 --> 00:06:35.259 a telling distinction. A role model is someone 00:06:35.259 --> 00:06:37.899 whose life path you want to emulate. To copy. 00:06:38.399 --> 00:06:41.600 Yonath had no interest in copying anyone. She 00:06:41.600 --> 00:06:43.819 was fascinated by the science, by the achievement, 00:06:44.060 --> 00:06:46.800 but she was determined to forge her own unique 00:06:46.800 --> 00:06:48.959 path. She didn't want to be the next Marie Curie. 00:06:49.079 --> 00:06:52.139 She wanted to be the first Ada Yonath. It's that 00:06:52.139 --> 00:06:55.000 fierce independence again. That I'll find my 00:06:55.000 --> 00:06:57.300 own way attitude. So she finishes high school, 00:06:57.459 --> 00:07:00.300 paying her way with math lessons, and then she 00:07:00.300 --> 00:07:02.519 heads back to Jerusalem for university. To the 00:07:02.519 --> 00:07:04.779 Hebrew University of Jerusalem. And she just 00:07:04.779 --> 00:07:06.939 flies through it. She gets her bachelor's degree 00:07:06.939 --> 00:07:10.019 in chemistry in 1962. Then she immediately gets 00:07:10.019 --> 00:07:12.879 a master's in biochemistry by 1964. So you can 00:07:12.879 --> 00:07:15.540 see her moving from the pure abstract chemistry 00:07:15.540 --> 00:07:19.279 into the chemistry of life itself. Exactly. And 00:07:19.279 --> 00:07:22.000 then comes the big pivot, the move that really 00:07:22.000 --> 00:07:25.459 defines her entire career. She goes to the Weizmann 00:07:25.459 --> 00:07:28.360 Institute of Science for her Ph .D. And her advisor 00:07:28.360 --> 00:07:31.600 there is a man named Wolfie Traub. Right. And 00:07:31.600 --> 00:07:33.399 the subject she takes on for her dissertation 00:07:33.399 --> 00:07:37.420 is the X -ray crystallography of collagen. OK, 00:07:37.500 --> 00:07:39.959 let's pause there. We need to break down X -ray 00:07:39.959 --> 00:07:41.899 crystallography because we're going to be hearing 00:07:41.899 --> 00:07:45.199 that term a lot. To the average person, I mean, 00:07:45.199 --> 00:07:46.579 that sounds like something out of science fiction. 00:07:46.639 --> 00:07:49.379 What is she actually doing? It really is a bit 00:07:49.379 --> 00:07:51.920 like science fiction. Okay, so imagine you have 00:07:51.920 --> 00:07:54.500 a tiny complex object like a protein molecule. 00:07:54.759 --> 00:07:56.800 You want to see its shape, but it's way, way 00:07:56.800 --> 00:07:59.319 too small for any normal microscope. Because 00:07:59.319 --> 00:08:01.379 it's smaller than the wavelength of visible light. 00:08:01.439 --> 00:08:04.000 Much smaller. A light wave just washes right 00:08:04.000 --> 00:08:06.620 over a protein like an ocean wave washing over 00:08:06.620 --> 00:08:08.779 a single grain of sand. You don't see the sand. 00:08:09.100 --> 00:08:11.560 So to see it, you need something with a much, 00:08:11.600 --> 00:08:14.560 much smaller wavelength. X -rays. But here's 00:08:14.560 --> 00:08:18.069 the problem. You can't focus x -rays with a lens 00:08:18.069 --> 00:08:20.750 like you can with light. There's no such thing 00:08:20.750 --> 00:08:22.810 as an x -ray microscope, so you have to do something 00:08:22.810 --> 00:08:26.009 clever. You take millions and millions of your 00:08:26.009 --> 00:08:28.189 protein molecules and you get them to line up 00:08:28.189 --> 00:08:31.029 perfectly, all facing the exact same direction 00:08:31.029 --> 00:08:34.389 in a repeating 3D pattern. You grow a crystal. 00:08:34.840 --> 00:08:37.720 Like a tiny, perfectly organized army of molecules. 00:08:38.000 --> 00:08:40.860 That's a perfect analogy. A regiment of soldiers 00:08:40.860 --> 00:08:43.840 on a parade ground. Then you take that crystal 00:08:43.840 --> 00:08:46.399 and you blast it with a powerful beam of x -rays. 00:08:46.519 --> 00:08:48.940 The x -rays hit the atoms in the crystal and 00:08:48.940 --> 00:08:51.139 they bounce off. They diffract. They scatter 00:08:51.139 --> 00:08:53.259 in a very specific pattern of spots that you 00:08:53.259 --> 00:08:55.639 capture on a detector behind the crystal. So 00:08:55.639 --> 00:08:57.360 you don't get a picture of the molecule itself, 00:08:57.460 --> 00:08:59.980 you just get... A pattern of dots? You get a 00:08:59.980 --> 00:09:01.600 diffraction pattern. It looks like a complex 00:09:01.600 --> 00:09:04.100 star map. And then, and this is the genius part, 00:09:04.279 --> 00:09:07.039 you use some very, very heavy mathematics, something 00:09:07.039 --> 00:09:09.799 called Fourier transforms, to work backwards 00:09:09.799 --> 00:09:12.200 from the pattern. You're reconstructing the object 00:09:12.200 --> 00:09:15.200 by analyzing its shadow. In a sense, yes. It's 00:09:15.200 --> 00:09:17.440 like being in a dark room with an invisible statue. 00:09:17.860 --> 00:09:20.220 You start throwing thousands of tennis balls 00:09:20.220 --> 00:09:22.720 at it, and you mark where every single ball hits 00:09:22.720 --> 00:09:25.019 the back wall. If you throw enough tennis balls, 00:09:25.139 --> 00:09:27.200 you can eventually figure out the exact shape. 00:09:27.799 --> 00:09:30.570 of the indisical statue. So for her Ph .D., she's 00:09:30.570 --> 00:09:33.110 throwing X -ray tennis balls at collagen. Exactly. 00:09:33.470 --> 00:09:37.129 Collagen is a fibrous structural protein. It's 00:09:37.129 --> 00:09:39.210 what keeps your skin elastic. She's learning 00:09:39.210 --> 00:09:41.730 the trade. She's figuring out how to grow the 00:09:41.730 --> 00:09:43.529 crystals, how to operate the X -ray machines, 00:09:43.870 --> 00:09:46.830 and crucially, how to do the math. And she gets 00:09:46.830 --> 00:09:49.769 her Ph .D. in 1968. She's officially Dr. Ada 00:09:49.769 --> 00:09:52.190 Yonath. She has the credentials. And so she heads 00:09:52.190 --> 00:09:54.870 to the U .S. for her postdoctoral work. She goes 00:09:54.870 --> 00:09:58.570 to Carnegie Mellon in 69 and then to MIT in 1960. 00:09:58.600 --> 00:10:00.759 I mean, this is the big leagues of science. While 00:10:00.759 --> 00:10:03.120 she's at MIT, she spends some time in a lab at 00:10:03.120 --> 00:10:05.080 Harvard that completely changes her trajectory. 00:10:05.580 --> 00:10:08.820 Yes, the lab of William N. Lipscomb Jr. He was 00:10:08.820 --> 00:10:11.320 an absolute giant in the field. He would go on 00:10:11.320 --> 00:10:13.320 to win the Nobel Prize in chemistry himself in 00:10:13.320 --> 00:10:16.000 1976. So she's seeing what's possible at the 00:10:16.000 --> 00:10:18.759 highest level. Right. Being in that environment, 00:10:18.899 --> 00:10:22.220 seeing these brilliant minds tackling enormous, 00:10:22.399 --> 00:10:25.460 seemingly impossible questions, it just emboldened 00:10:25.460 --> 00:10:28.240 her. She starts thinking, you know, about... 00:10:28.539 --> 00:10:32.019 very large structures. Why is large a scary word 00:10:32.019 --> 00:10:34.960 in crystallography? Intuitively, I think a bigger 00:10:34.960 --> 00:10:37.000 object would be easier to see than a tiny one. 00:10:37.120 --> 00:10:40.299 That's logical, but in biology, large almost 00:10:40.299 --> 00:10:43.620 always means complex, and more importantly, unstable. 00:10:44.399 --> 00:10:46.820 What do you mean by unstable? Well, a small molecule 00:10:46.820 --> 00:10:49.799 like salt is like a hard, rigid little brick. 00:10:49.980 --> 00:10:52.240 It's easy to stack them into a perfect crystal. 00:10:52.679 --> 00:10:55.539 But large biological machines, like the one she 00:10:55.539 --> 00:10:57.259 was getting interested in, they're floppy. They 00:10:57.259 --> 00:10:59.139 have moving parts. They're flexible. They don't 00:10:59.139 --> 00:11:01.259 want to hold still and line up in a perfect crystal 00:11:01.259 --> 00:11:03.259 lattice. But that's exactly what Yonath decided 00:11:03.259 --> 00:11:05.779 she wants to tackle. The biggest, floppiest machine 00:11:05.779 --> 00:11:09.120 of all. The ribosome. That's right. She returns 00:11:09.120 --> 00:11:12.419 to Israel in 1970. And she establishes the very 00:11:12.419 --> 00:11:15.340 first protein crystallography laboratory in the 00:11:15.340 --> 00:11:17.740 entire country. The first one. The first one. 00:11:18.080 --> 00:11:20.379 And for nearly a decade, it would be the only 00:11:20.379 --> 00:11:23.679 one. She is a complete lone wolf building this 00:11:23.679 --> 00:11:25.879 entire field of science from the ground up in 00:11:25.879 --> 00:11:28.279 Israel. And she sets her sights on the ribosome. 00:11:28.399 --> 00:11:30.460 Okay, let's define the target. We know it's a 00:11:30.460 --> 00:11:33.480 very large structure. But what is its actual 00:11:33.480 --> 00:11:35.840 job? What does the ribosome do that makes it 00:11:35.840 --> 00:11:38.700 worth all this effort? The ribosome is... It's 00:11:38.700 --> 00:11:41.779 the universal translator of life. Your DNA contains 00:11:41.779 --> 00:11:44.159 all the instructions to build you, your eye color, 00:11:44.279 --> 00:11:46.559 your hair color, how to digest your lunch. But 00:11:46.559 --> 00:11:48.940 the DNA itself is just a library. It just sits 00:11:48.940 --> 00:11:51.039 there. It doesn't actually do anything. It's 00:11:51.039 --> 00:11:53.720 passive. It's passive. The ribosome is the machine 00:11:53.720 --> 00:11:55.899 that comes in, takes a working copy of those 00:11:55.899 --> 00:11:58.720 instructions, a molecule called RNA, and it reads 00:11:58.720 --> 00:12:00.980 them. And as it reads the instructions, it simultaneously 00:12:00.980 --> 00:12:03.580 builds what the instructions describe. It builds 00:12:03.580 --> 00:12:07.200 proteins? It builds proteins. And proteins are, 00:12:07.360 --> 00:12:10.549 for all - practical purposes, everything. Hemoglobin, 00:12:10.610 --> 00:12:12.929 the molecule that carries oxygen in your blood. 00:12:12.970 --> 00:12:16.649 That's a protein. Insulin is a protein. The antibodies 00:12:16.649 --> 00:12:19.149 fighting off your cold are proteins. The keratin 00:12:19.149 --> 00:12:21.889 in your hair and fingernails is a protein. The 00:12:21.889 --> 00:12:24.090 ribosome is the single machine that makes all 00:12:24.090 --> 00:12:26.370 of them. So if it stops working? You stop working 00:12:26.370 --> 00:12:30.090 instantly. Without the ribosome, life as we know 00:12:30.090 --> 00:12:32.889 it is impossible. It is arguably the most important 00:12:32.889 --> 00:12:36.399 single piece of machinery in your body. And Yonath 00:12:36.399 --> 00:12:38.639 wanted to know how it worked, to pop the hood 00:12:38.639 --> 00:12:40.799 and see the engine. Exactly. And to know how 00:12:40.799 --> 00:12:42.659 any machine works, you first have to know what 00:12:42.659 --> 00:12:44.600 it looks like. You need the blueprint. But when 00:12:44.600 --> 00:12:46.899 she started telling people, hey, I'm going to 00:12:46.899 --> 00:12:48.940 crystallize the ribosome and get its structure, 00:12:49.120 --> 00:12:52.720 the reaction wasn't, you know. Great idea. Good 00:12:52.720 --> 00:12:55.080 luck. No. The reaction was, you're wasting your 00:12:55.080 --> 00:12:57.299 time. The notes used the phrase considerable 00:12:57.299 --> 00:12:59.779 skepticism. Which we already established is polite 00:12:59.779 --> 00:13:02.860 speech. Right. In reality, it was outright dismissal. 00:13:02.860 --> 00:13:04.519 People thought she was on a fool's errand. They 00:13:04.519 --> 00:13:07.720 thought it was a career -ending move. Why? What 00:13:07.720 --> 00:13:10.179 was it about the ribosome that made it so much 00:13:10.179 --> 00:13:12.899 harder than, say, the collagen she studied for 00:13:12.899 --> 00:13:16.580 her PhD? A few really big things. First, as we 00:13:16.580 --> 00:13:18.879 said, it's just massive. It's an enormous complex. 00:13:19.620 --> 00:13:22.340 Second, it's not made of just one thing. It's 00:13:22.340 --> 00:13:25.179 a messy mixture of RNA and protein, which makes 00:13:25.179 --> 00:13:27.799 its chemistry very complicated. Okay. And third, 00:13:28.019 --> 00:13:30.120 and this is the real killer, it's incredibly 00:13:30.120 --> 00:13:33.879 flexible. It has to move to do its job. So trying 00:13:33.879 --> 00:13:36.059 to get millions of these things to sit perfectly 00:13:36.059 --> 00:13:38.200 still on a crystal was, and I'm not exaggerating, 00:13:38.259 --> 00:13:41.059 like trying to stack a million live jellyfish 00:13:41.059 --> 00:13:43.460 into a perfect pyramid. They just slide and wobble. 00:13:43.529 --> 00:13:45.470 Squashed. They squash. They don't cooperate. 00:13:45.830 --> 00:13:48.370 And if your molecules are wobbling even a tiny 00:13:48.370 --> 00:13:51.009 bit in the crystal, your X -ray picture is just 00:13:51.009 --> 00:13:54.470 a blurry mess. You get nothing. Worse than nothing. 00:13:54.470 --> 00:13:57.070 You just get noise. So she spends how long? How 00:13:57.070 --> 00:13:59.190 many years is she trying to stack these jellyfish? 00:13:59.450 --> 00:14:02.950 Almost 20 years. 20 years. From the time she 00:14:02.950 --> 00:14:05.350 seriously started the project in the late 70s 00:14:05.350 --> 00:14:07.470 until she published the final high resolution 00:14:07.470 --> 00:14:10.029 structure, it was a two decade long journey. 00:14:10.509 --> 00:14:12.889 That's an entire scientific career for most people. 00:14:12.990 --> 00:14:14.850 For a lot of that time, she was just fighting 00:14:14.850 --> 00:14:17.610 constant failure. She had managed to grow some 00:14:17.610 --> 00:14:20.929 crystals, but they'd be tiny and flawed. Or they 00:14:20.929 --> 00:14:22.909 would dissolve as soon as she looked at them. 00:14:23.029 --> 00:14:25.850 Or, and this was the big one, the X -rays themselves 00:14:25.850 --> 00:14:28.929 would destroy them. Ah, right. That's the other 00:14:28.929 --> 00:14:31.110 problem here, isn't it? The tool you're using 00:14:31.110 --> 00:14:33.669 to see the thing is also the tool that's destroying 00:14:33.669 --> 00:14:36.970 it. It's the ultimate catch -22 of crystallography. 00:14:37.529 --> 00:14:40.629 To see the atoms clearly, you need a really powerful 00:14:40.629 --> 00:14:43.950 high -energy X -ray beam. But high -energy X 00:14:43.950 --> 00:14:46.429 -rays are ionizing radiation. They literally 00:14:46.429 --> 00:14:49.450 cook biological matter. They snap chemical bonds. 00:14:49.769 --> 00:14:52.710 So the very act of taking the picture is incinerating 00:14:52.710 --> 00:14:54.789 your subject. Precisely. You'd turn on the beam, 00:14:54.909 --> 00:14:56.629 you'd get maybe a split second of data, and then 00:14:56.629 --> 00:14:58.529 your beautiful, precious crystal would just turn 00:14:58.529 --> 00:15:00.789 to mush. You could never collect enough data 00:15:00.789 --> 00:15:03.149 from a single crystal to build the full 3D model. 00:15:03.350 --> 00:15:05.789 It really seemed like a fundamental law of physics 00:15:05.789 --> 00:15:08.350 was standing in their way. And this is the moment 00:15:08.350 --> 00:15:11.289 where Ada Yonath stops being just a persistent, 00:15:11.470 --> 00:15:14.029 stubborn scientist and becomes a true inventor. 00:15:14.250 --> 00:15:16.669 She comes up with a solution that nobody else 00:15:16.669 --> 00:15:20.009 had seriously considered. Cryo -biocrystallography. 00:15:20.190 --> 00:15:23.269 She freezes it. It sounds so simple when you 00:15:23.269 --> 00:15:25.350 say it like that, right? If the thing is burning 00:15:25.350 --> 00:15:28.570 up, just cool it down. But it's not as simple 00:15:28.570 --> 00:15:31.190 as putting it in your kitchen freezer. What happens 00:15:31.190 --> 00:15:33.960 when you freeze water normally? It turns into 00:15:33.960 --> 00:15:37.200 ice. It turns into ice and ice expands. And more 00:15:37.200 --> 00:15:40.100 importantly, ice crystals are sharp, jagged things. 00:15:40.299 --> 00:15:43.179 Yeah. If you let sharp ice crystals form inside 00:15:43.179 --> 00:15:45.899 your delicate, perfectly ordered ribosome crystal. 00:15:46.139 --> 00:15:47.860 It would shatter it from the inside out. And 00:15:47.860 --> 00:15:50.259 a grenade going off inside it. So you can't have 00:15:50.259 --> 00:15:52.840 ice, but you still have to be frozen solid. That 00:15:52.840 --> 00:15:54.679 sounds like a paradox. It is, but she solved 00:15:54.679 --> 00:15:57.539 it. The solution is called vitrification. You 00:15:57.539 --> 00:16:00.039 have to cool the crystal so incredibly fast, 00:16:00.120 --> 00:16:02.059 we're talking about flash freezing, that the 00:16:02.059 --> 00:16:04.039 water molecules literally don't have time to 00:16:04.039 --> 00:16:06.100 arrange themselves into the structure of an ice 00:16:06.100 --> 00:16:07.820 crystal. They just stop moving right where they 00:16:07.820 --> 00:16:10.860 are. So the water becomes a solid, but without 00:16:10.860 --> 00:16:14.059 the crystal structure. It forms a glass, a solid 00:16:14.059 --> 00:16:17.379 amorphous state. She developed this whole technique 00:16:17.379 --> 00:16:19.980 of looping out a crystal and plunging it into 00:16:19.980 --> 00:16:22.679 liquid nitrogen or liquid propane at incredibly 00:16:22.679 --> 00:16:25.700 specific speeds and temperatures to achieve this 00:16:25.700 --> 00:16:28.340 glassy state. And what she discovered was that 00:16:28.340 --> 00:16:30.720 at these cryogenic temperatures, we're talking 00:16:30.720 --> 00:16:34.200 around minus 185 degrees Celsius, the crystals 00:16:34.200 --> 00:16:36.379 became incredibly tough. They could withstand 00:16:36.379 --> 00:16:38.600 the radiation. They could take the full blast 00:16:38.600 --> 00:16:41.340 of the X -ray beam for much, much longer, long 00:16:41.340 --> 00:16:43.899 enough finally to collect a complete data set. 00:16:44.220 --> 00:16:46.259 And this technique, this wasn't just a solution 00:16:46.259 --> 00:16:48.740 for her ribosome problem. No, this was a revolution 00:16:48.740 --> 00:16:51.820 for the entire field. Suddenly, all those other 00:16:51.820 --> 00:16:55.019 impossible large structures, huge viruses, complex 00:16:55.019 --> 00:16:57.879 enzyme assemblies, they all became possible targets. 00:16:58.159 --> 00:17:00.299 She gave the entire field of structural biology 00:17:00.299 --> 00:17:03.620 a new superpower. So today this is standard practice. 00:17:03.840 --> 00:17:06.359 Oh, completely routine. Every structural biology 00:17:06.359 --> 00:17:09.279 lab in the world uses cryocrystallography now. 00:17:09.440 --> 00:17:11.599 But they use it because she had to invent it 00:17:11.599 --> 00:17:14.519 to solve her own unsolvable problem. So she has 00:17:14.519 --> 00:17:16.539 the method. She can freeze the crystals. She 00:17:16.539 --> 00:17:18.119 can hit them with the beam. She can collect the 00:17:18.119 --> 00:17:20.500 data. And then finally, around the years 2000 00:17:20.500 --> 00:17:23.940 and 2001, she gets the picture. She gets the 00:17:23.940 --> 00:17:27.660 picture. She publishes the complete high -resolution 00:17:27.660 --> 00:17:30.920 atomic structures of both of the ribosomal subunits. 00:17:31.039 --> 00:17:32.799 Wait, there are two parts to it. That's right. 00:17:32.900 --> 00:17:35.279 The ribosome is made of two pieces that clamp 00:17:35.279 --> 00:17:38.460 together. There's a small subunit whose job is 00:17:38.460 --> 00:17:41.160 to read and decode the RNA instruction sheet. 00:17:41.319 --> 00:17:43.440 And then there's a large subunit, which is the 00:17:43.440 --> 00:17:46.099 part that actually builds the new protein chain. 00:17:46.319 --> 00:17:48.480 She mapped both of them. So the 20 -year quest 00:17:48.480 --> 00:17:51.220 is over. She opens up the black box. And when 00:17:51.220 --> 00:17:54.599 she looks at this map, this 3D landscape of atoms, 00:17:54.740 --> 00:17:57.700 what does she see? What were the big aha moments? 00:17:57.980 --> 00:18:00.859 The biggest, most profound discovery was deep 00:18:00.859 --> 00:18:04.069 inside the core of the large subunit. She found 00:18:04.069 --> 00:18:06.869 this one specific pocket, a region she called 00:18:06.869 --> 00:18:09.390 the universal symmetrical region. Universal as 00:18:09.390 --> 00:18:11.930 in, it's in everything. As in, it is identical 00:18:11.930 --> 00:18:14.309 in you, in me, in the bacteria on your skin, 00:18:14.529 --> 00:18:17.750 in a yeast cell, in an elephant, in a tree. It 00:18:17.750 --> 00:18:20.130 has not changed in billions of years of evolution. 00:18:20.430 --> 00:18:22.410 That implies that it must be the oldest part, 00:18:22.549 --> 00:18:25.319 the original engine. That's exactly what it implies. 00:18:25.660 --> 00:18:28.740 She had very likely found the protoribosome, 00:18:28.880 --> 00:18:31.259 the ancient original machine that first allowed 00:18:31.259 --> 00:18:34.079 life to reliably build proteins from a set of 00:18:34.079 --> 00:18:36.579 instructions. It's like finding a fossil, but 00:18:36.579 --> 00:18:38.619 it's a molecular fossil from the dawn of life. 00:18:38.759 --> 00:18:41.440 That gives me chills. She's literally looking 00:18:41.440 --> 00:18:44.920 at a piece of machinery that is maybe three billion 00:18:44.920 --> 00:18:48.140 years old. And that's not all. This region revealed 00:18:48.140 --> 00:18:50.920 something else that settled a huge, longstanding 00:18:50.920 --> 00:18:54.019 debate in biology. For years, scientists had 00:18:54.019 --> 00:18:55.940 argued about what was actually doing the work 00:18:55.940 --> 00:18:58.579 in the ribosome. Was it the proteins in the complex 00:18:58.579 --> 00:19:00.799 or was it the RNA? The smart money would have 00:19:00.799 --> 00:19:02.200 been on the proteins, right? I mean, proteins 00:19:02.200 --> 00:19:04.579 are the workers of the cell. All the enzymes 00:19:04.579 --> 00:19:07.039 that do chemistry are proteins. That was the 00:19:07.039 --> 00:19:09.960 central dogma. But what Ada's structure showed 00:19:09.960 --> 00:19:13.519 with irrefutable clarity was that in the absolute 00:19:13.519 --> 00:19:15.779 heart of the machine, the spot where the new 00:19:15.779 --> 00:19:18.200 chemical bonds are actually being formed to link 00:19:18.200 --> 00:19:21.359 the protein chain together. There are no proteins. 00:19:21.539 --> 00:19:24.359 None at all. It's all RNA. So the RNA is the 00:19:24.359 --> 00:19:27.140 engine. The RNA is the engine. The proteins are 00:19:27.140 --> 00:19:29.140 just the scaffolding on the outside holding it 00:19:29.140 --> 00:19:32.019 all in the right shape. She proved definitively 00:19:32.019 --> 00:19:35.880 that the ribosome is a ribosome, an enzyme made 00:19:35.880 --> 00:19:38.680 of RNA. This completely flips the script on the 00:19:38.680 --> 00:19:40.799 old chicken or the egg problem of the origin 00:19:40.799 --> 00:19:42.960 of life. It's the strongest evidence we have 00:19:42.960 --> 00:19:46.039 for the RNA world hypothesis. The idea that early 00:19:46.039 --> 00:19:49.289 in life's history, RNA came first. RNA was the 00:19:49.289 --> 00:19:51.529 molecule that could both store information like 00:19:51.529 --> 00:19:55.069 DNA and do chemical work like a protein. DNA 00:19:55.069 --> 00:19:57.250 and proteins evolved later. And he also found 00:19:57.250 --> 00:20:00.529 a tunnel. The source material mentions the ribosomal 00:20:00.529 --> 00:20:03.789 tunnel. Ah, yes, the tunnel. I love this part. 00:20:04.130 --> 00:20:07.049 Describe what that is. So as the ribosome is 00:20:07.049 --> 00:20:09.329 knitting together these amino acids one by one, 00:20:09.369 --> 00:20:11.789 it's creating a long growing chain, a little 00:20:11.789 --> 00:20:14.170 protein tail. And that tail has to go somewhere 00:20:14.170 --> 00:20:17.109 while it's being made. Yoneth's structure revealed 00:20:17.109 --> 00:20:20.009 a physical tunnel about 100 angstroms long that 00:20:20.009 --> 00:20:22.210 runs right through the middle of the large subunit. 00:20:22.230 --> 00:20:24.309 It's the exit chute. It's like a birth canal 00:20:24.309 --> 00:20:26.829 for every new protein. It is exactly like a birth 00:20:26.829 --> 00:20:29.230 canal. But what she found later in even more 00:20:29.230 --> 00:20:31.690 detailed studies is that it's not just a passive 00:20:31.690 --> 00:20:34.190 pipe. The walls of the tunnel are active. They 00:20:34.190 --> 00:20:37.230 have gating mechanisms. The tunnel actually interacts 00:20:37.230 --> 00:20:39.589 with the new protein as it passes through. So 00:20:39.589 --> 00:20:42.000 it can... What, check the protein for quality? 00:20:42.299 --> 00:20:44.539 It can pause the whole process. It plays a role 00:20:44.539 --> 00:20:47.359 in regulation. She showed that there are dynamic 00:20:47.359 --> 00:20:49.319 elements in the tunnel involved in something 00:20:49.319 --> 00:20:52.420 called elongation arrest. It's an intelligent 00:20:52.420 --> 00:20:55.660 tunnel. It can sense what it's making and tell 00:20:55.660 --> 00:20:57.839 the factory floor to stop if there's a problem. 00:20:58.039 --> 00:21:00.940 That's unbelievably sophisticated. And we only 00:21:00.940 --> 00:21:02.619 know any of this because you figured out how 00:21:02.619 --> 00:21:04.319 to freeze it and take its picture. We had no 00:21:04.319 --> 00:21:07.099 idea before that. Okay, so... We've got the origin 00:21:07.099 --> 00:21:09.319 of life. We've got the RNA world. We've got this 00:21:09.319 --> 00:21:11.400 intelligent protein tunnel. This is obviously 00:21:11.400 --> 00:21:14.880 huge for fundamental basic science. But you said 00:21:14.880 --> 00:21:16.880 at the beginning that this work also transformed 00:21:16.880 --> 00:21:19.799 medicine. How do we get from a frozen crystal 00:21:19.799 --> 00:21:23.180 in a lab in Israel to, you know, a pill that 00:21:23.180 --> 00:21:25.180 I take for strep throat? This is where the story 00:21:25.180 --> 00:21:27.140 becomes incredibly practical. This brings us 00:21:27.140 --> 00:21:30.299 to antibiotics. We all take them, but I would 00:21:30.299 --> 00:21:32.319 guess most people have no idea how they actually 00:21:32.319 --> 00:21:35.160 work on a molecular level. Well, a huge class 00:21:35.160 --> 00:21:37.259 of our most important antibiotics, things like 00:21:37.259 --> 00:21:39.700 erythromycin, which is in the Z -Pak you take, 00:21:39.920 --> 00:21:42.759 clindamycin, tetracyclines, they all work by 00:21:42.759 --> 00:21:45.779 doing one thing. They attack the ribosome. They 00:21:45.779 --> 00:21:48.500 shut down the bacteria's protein factory. Exactly. 00:21:48.920 --> 00:21:51.160 If you shut down the factory, the bacteria can't 00:21:51.160 --> 00:21:53.240 build new parts. It can't repair itself. It can't 00:21:53.240 --> 00:21:56.059 reproduce. It just dies. But here's the obvious 00:21:56.059 --> 00:21:59.700 question. I have ribosomes. You have ribosomes. 00:22:00.200 --> 00:22:02.859 Trillions of them. Why doesn't the Z -Pak shut 00:22:02.859 --> 00:22:05.619 down my protein factories and kill me? That is 00:22:05.619 --> 00:22:08.380 the multi -billion dollar question in pharmacology. 00:22:08.500 --> 00:22:11.500 It's called selectivity. And for decades before 00:22:11.500 --> 00:22:13.579 Yonath, we knew that it worked, but we didn't 00:22:13.579 --> 00:22:15.019 really know why it worked. It was a bit of a 00:22:15.019 --> 00:22:16.980 mystery. We just knew through trial and error, 00:22:17.079 --> 00:22:19.640 this chemical kills bacteria, but it doesn't 00:22:19.640 --> 00:22:21.960 kill human cells. And Yonath's structure showed 00:22:21.960 --> 00:22:24.680 us the why. She showed us the why at the atomic 00:22:24.680 --> 00:22:27.240 level. She demonstrated that while that deep 00:22:27.240 --> 00:22:30.500 universal core is the same in all life, the outer 00:22:30.500 --> 00:22:32.500 parts of the ribosome, the parts that are more 00:22:32.500 --> 00:22:35.279 exposed, have tiny but significant structural 00:22:35.279 --> 00:22:38.799 differences between bacteria and humans. So the 00:22:38.799 --> 00:22:41.640 lock on the bacterial ribosome is a slightly 00:22:41.640 --> 00:22:44.500 different shape from the lock on the human ribosome. 00:22:44.599 --> 00:22:46.720 That's the perfect way to put it. And an antibiotic 00:22:46.720 --> 00:22:49.279 molecule is like a key that is shaped to fit 00:22:49.279 --> 00:22:52.630 only the bacterial lock. Yoneth went on to map 00:22:52.630 --> 00:22:55.009 the exact binding sites of over 20 different 00:22:55.009 --> 00:22:58.289 antibiotics. She showed us precisely where the 00:22:58.289 --> 00:23:00.730 drug molecule wedges itself into the bacterial 00:23:00.730 --> 00:23:03.450 ribosome's machinery to jam the gears. She showed 00:23:03.450 --> 00:23:05.170 us where to stick the wrench. Not just that. 00:23:05.549 --> 00:23:07.410 Even more importantly, she showed us how the 00:23:07.410 --> 00:23:10.440 gears learn to fight back. She illuminated the 00:23:10.440 --> 00:23:12.799 mechanisms of antibiotic resistance. Which is 00:23:12.799 --> 00:23:14.720 the huge crisis we're facing now where the drugs 00:23:14.720 --> 00:23:16.980 stop working. Right. And because we now have 00:23:16.980 --> 00:23:19.259 the high -resolution structure, we can see resistance 00:23:19.259 --> 00:23:22.000 happening at an atomic level. For example, a 00:23:22.000 --> 00:23:24.880 bacteria might evolve to change one single atom 00:23:24.880 --> 00:23:27.240 on the wall of the ribosomal tunnel. Just one 00:23:27.240 --> 00:23:29.940 tiny change. And suddenly the drug doesn't fit 00:23:29.940 --> 00:23:32.079 anymore. Suddenly the drug can't latch on as 00:23:32.079 --> 00:23:34.660 tightly. It just slips off. The wrench can't 00:23:34.660 --> 00:23:39.119 get a grip. So resistance is just... a tiny structural 00:23:39.119 --> 00:23:42.740 renovation project by the bacteria. It's molecular 00:23:42.740 --> 00:23:44.980 redecorating to kick out the unwelcome guest. 00:23:45.259 --> 00:23:48.119 And this is the game changer. Because Yonath 00:23:48.119 --> 00:23:50.660 gave us the blueprint, drug companies can now 00:23:50.660 --> 00:23:53.700 look at that newly renovated resistant ribosome 00:23:53.700 --> 00:23:56.640 and say, okay, the bacteria changed this part 00:23:56.640 --> 00:23:58.819 of the lock. Let's go back to the lab and design 00:23:58.819 --> 00:24:01.660 a brand new key that fits this new lock. This 00:24:01.660 --> 00:24:04.220 is what they call structure -based drug design. 00:24:04.569 --> 00:24:06.430 That's it. It takes so much of the guesswork 00:24:06.430 --> 00:24:08.289 out of it. Instead of just randomly screening 00:24:08.289 --> 00:24:10.650 thousands of chemicals in a petri dish, hoping 00:24:10.650 --> 00:24:13.230 one works, it becomes a rational engineering 00:24:13.230 --> 00:24:15.950 problem. You can literally design a new drug 00:24:15.950 --> 00:24:18.430 on a computer to fit perfectly into the target 00:24:18.430 --> 00:24:20.869 pocket you can now see. So you can design drugs 00:24:20.869 --> 00:24:23.529 that are more powerful or that specifically overcome 00:24:23.529 --> 00:24:26.549 known resistance mechanisms. Exactly. So if you 00:24:26.549 --> 00:24:28.890 or anyone you know has been cured of a nasty 00:24:28.890 --> 00:24:31.650 bacterial infection in the last 20 years, you 00:24:31.650 --> 00:24:34.289 owe a direct debt of gratitude to Ada Yanis' 00:24:34.369 --> 00:24:37.109 decades of work in that lab. It's just the ultimate 00:24:37.109 --> 00:24:39.789 vindication, isn't it? The formidable, impossible 00:24:39.789 --> 00:24:42.269 project that everyone told her would be a waste 00:24:42.269 --> 00:24:45.769 of time ends up providing the tools to save millions 00:24:45.769 --> 00:24:47.920 of lives. And, you know, the world eventually 00:24:47.920 --> 00:24:50.799 caught on. It took a while. But in 2009, the 00:24:50.799 --> 00:24:53.599 phone call finally came from Stockholm. The Nobel 00:24:53.599 --> 00:24:55.980 Prize in Chemistry. She shared it with two other 00:24:55.980 --> 00:24:58.960 scientists, Venkatraman Ramakrishnan and Thomas 00:24:58.960 --> 00:25:01.640 Stites, who also did incredible work on the ribosome. 00:25:02.220 --> 00:25:05.160 But her win was especially historic for a number 00:25:05.160 --> 00:25:07.240 of reasons. Let's run through the stats on this 00:25:07.240 --> 00:25:10.140 because they're pretty staggering. OK, so she 00:25:10.140 --> 00:25:13.240 was the first Israeli woman. ever to win a Nobel 00:25:13.240 --> 00:25:15.940 Prize in any category. Wow. She was the first 00:25:15.940 --> 00:25:17.859 woman from anywhere in the Middle East to win 00:25:17.859 --> 00:25:20.319 a Nobel Prize in the sciences. That is a huge 00:25:20.319 --> 00:25:22.799 milestone for the region. But look at the gender 00:25:22.799 --> 00:25:25.880 gap in her specific field. This one is amazing. 00:25:26.119 --> 00:25:29.059 She was the first woman in 45 years to win the 00:25:29.059 --> 00:25:31.980 Nobel Prize in chemistry. 45 years? Are you serious? 00:25:32.259 --> 00:25:34.980 The last woman to win it before her was Dorothy 00:25:34.980 --> 00:25:38.880 Hodgkin, all the way back in 1964. That is just 00:25:38.880 --> 00:25:41.549 a staggeringly long drought. It really puts into 00:25:41.549 --> 00:25:44.089 perspective what she was up against. The kind 00:25:44.089 --> 00:25:47.170 of boys club that field must have been for decades. 00:25:47.490 --> 00:25:49.730 She didn't just break the glass ceiling. She 00:25:49.730 --> 00:25:52.779 crystallized it and shot x -rays at it. And it 00:25:52.779 --> 00:25:55.000 wasn't just the Nobel, was it? The awards just 00:25:55.000 --> 00:25:57.960 started pouring in. She essentially won every 00:25:57.960 --> 00:26:00.759 major prize there is to win in science. Pretty 00:26:00.759 --> 00:26:03.539 much. The Wolf Prize, which is a huge honor. 00:26:03.720 --> 00:26:07.480 The Harvey Prize. The L 'Oreal UNESCO Award for 00:26:07.480 --> 00:26:10.160 Women in Science. Even Pope Francis got in on 00:26:10.160 --> 00:26:12.700 it. He named her as a member of the Pontifical 00:26:12.700 --> 00:26:15.799 Academy of Sciences in 2014. Which is a fascinating 00:26:15.799 --> 00:26:18.339 appointment for a Jewish scientist from Israel. 00:26:18.559 --> 00:26:21.220 It just shows that great science transcends all 00:26:21.220 --> 00:26:23.549 of those borders. And the honorary doctorates, 00:26:23.630 --> 00:26:25.930 she has them from all over the world, France, 00:26:26.210 --> 00:26:29.349 Poland, the UK, the Philippines. And in a really 00:26:29.349 --> 00:26:31.490 nice full circle moment, Carnegie Mellon, where 00:26:31.490 --> 00:26:34.269 she was just a visiting postdoc back in 69, gave 00:26:34.269 --> 00:26:36.970 her an honorary doctorate in 2018. From a visiting 00:26:36.970 --> 00:26:39.069 researcher to a living legend. It's a pretty 00:26:39.069 --> 00:26:41.009 amazing arc. We've spent a lot of time on the 00:26:41.009 --> 00:26:43.269 scientist and rightly so. But I want to spend 00:26:43.269 --> 00:26:46.869 a minute on the person because she isn't just 00:26:46.869 --> 00:26:49.690 a brain in a lab. She's a mother, a grandmother. 00:26:49.869 --> 00:26:52.910 Yes, she has. One daughter, Hajit Yonath, who 00:26:52.910 --> 00:26:55.670 is a doctor at a major Israeli hospital. So the 00:26:55.670 --> 00:26:57.549 healing profession clearly runs in the family. 00:26:57.690 --> 00:27:00.190 And she has a granddaughter named Noah. And she's 00:27:00.190 --> 00:27:03.630 also someone who lives in a very complex and 00:27:03.630 --> 00:27:06.890 fraught part of the world. She's in Israel. And 00:27:06.890 --> 00:27:09.190 she hasn't been silent about her views on the 00:27:09.190 --> 00:27:11.829 political situation there. No, she hasn't. And 00:27:11.829 --> 00:27:13.390 we should be careful here just to report what 00:27:13.390 --> 00:27:16.210 the sources say her stance is, not to interpret 00:27:16.210 --> 00:27:18.490 it. But yes, she has been quite vocal about the 00:27:18.490 --> 00:27:20.869 Israeli -Palestinian conflict, specifically on 00:27:20.869 --> 00:27:23.109 the issue of prisoners. And what is her stated 00:27:23.109 --> 00:27:25.849 position? She has publicly called for the unconditional 00:27:25.849 --> 00:27:29.109 release of all Palestinian prisoners held by 00:27:29.109 --> 00:27:31.849 Israel. That is a very controversial stance to 00:27:31.849 --> 00:27:33.750 take within Israel, I would imagine. What's her 00:27:33.750 --> 00:27:36.029 reasoning? Her logic seems to be very pragmatic, 00:27:36.190 --> 00:27:39.109 actually. It's almost scientific. She looks at 00:27:39.109 --> 00:27:41.670 the mechanism of the conflict. She argues that 00:27:41.670 --> 00:27:44.009 as long as Israel holds Palestinian prisoners, 00:27:44.369 --> 00:27:47.410 it provides a powerful motivation for militant 00:27:47.410 --> 00:27:50.109 groups to kidnap Israeli soldiers. To use them 00:27:50.109 --> 00:27:51.829 as bargaining chips. To use them as bargaining 00:27:51.829 --> 00:27:55.069 chips for a prisoner exchange. Exactly. So her 00:27:55.069 --> 00:27:57.609 argument is if you remove the prisoners from 00:27:57.609 --> 00:28:00.309 the equation, you remove the primary incentive 00:28:00.309 --> 00:28:03.069 for kidnapping. The quote from her is, once we 00:28:03.069 --> 00:28:05.269 don't have any prisoners to release, they will 00:28:05.269 --> 00:28:08.890 have no reason to kidnap soldiers. Yes. And whether 00:28:08.890 --> 00:28:11.000 you agree or disagree. with that geopolitical 00:28:11.000 --> 00:28:13.180 analysis, it's fascinating to see that same kind 00:28:13.180 --> 00:28:15.859 of thinking. She looks at a complex system, a 00:28:15.859 --> 00:28:18.319 cycle of violence, and she asks, what is the 00:28:18.319 --> 00:28:20.740 underlying mechanism driving this? How can we 00:28:20.740 --> 00:28:22.940 break the machine? It's the same mind that looked 00:28:22.940 --> 00:28:26.259 at the ribosome. Exactly. In the lab, she debugs 00:28:26.259 --> 00:28:28.880 the ribosome's translation process. In the world, 00:28:28.960 --> 00:28:31.140 she tries to debug the incentive structure of 00:28:31.140 --> 00:28:33.339 conflict. It's also worth noting that activism 00:28:33.339 --> 00:28:36.539 seems to run in the family. Her cousin is Rukama 00:28:36.539 --> 00:28:39.670 Martin, a very famous Israeli anti - occupation 00:28:39.670 --> 00:28:42.109 activist. So we've gone on this journey from 00:28:42.109 --> 00:28:44.569 a little girl reading books in a crowded Jerusalem 00:28:44.569 --> 00:28:47.809 apartment to a Nobel laureate who mapped the 00:28:47.809 --> 00:28:51.089 atomic machinery of life. When you step back 00:28:51.089 --> 00:28:53.210 from all the details, from the x -rays and the 00:28:53.210 --> 00:28:55.869 cryo cooling, what's the big takeaway for you 00:28:55.869 --> 00:28:58.680 from her story? For me, it's a profound lesson 00:28:58.680 --> 00:29:01.460 about the importance of basic science. What do 00:29:01.460 --> 00:29:03.640 you mean by that? Ada Yonath didn't start this 00:29:03.640 --> 00:29:06.160 project because she wanted to invent a better 00:29:06.160 --> 00:29:09.059 antibiotic. She wasn't trying to cure anything. 00:29:09.240 --> 00:29:12.400 She was driven by pure, fundamental curiosity. 00:29:12.859 --> 00:29:16.039 She just wanted to know. What does this beautiful 00:29:16.039 --> 00:29:19.059 essential machine look like? She was chasing 00:29:19.059 --> 00:29:21.819 knowledge for its own sake. Yes. And today, you 00:29:21.819 --> 00:29:23.980 know, funding agencies and governments, they're 00:29:23.980 --> 00:29:26.460 often so focused on applied science. They want 00:29:26.460 --> 00:29:28.579 to know if we give you this research grant, what 00:29:28.579 --> 00:29:30.579 product will we have in three years? What's the 00:29:30.579 --> 00:29:32.940 immediate return on investment? And if Jonas 00:29:32.940 --> 00:29:35.259 had to answer that question in 1980, she would 00:29:35.259 --> 00:29:37.180 have had nothing. She would have had nothing 00:29:37.180 --> 00:29:39.319 to say. She was just trying to take a picture 00:29:39.319 --> 00:29:42.359 of a jellyfish pyramid. But because she was allowed 00:29:42.359 --> 00:29:45.579 to pursue that useless fundamental question for 00:29:45.579 --> 00:29:49.200 20 years, we got the cures. We got the new drugs. 00:29:49.500 --> 00:29:51.519 The applications follow the understanding. They 00:29:51.519 --> 00:29:54.480 have to. You cannot fix what you do not understand. 00:29:54.740 --> 00:29:57.079 You have to be willing to do the deep, slow, 00:29:57.299 --> 00:30:00.160 patient work of just figuring out how nature 00:30:00.160 --> 00:30:02.259 works first. And the other takeaway has to be 00:30:02.259 --> 00:30:05.980 just that. Yeah. That resilience, that stubbornness 00:30:05.980 --> 00:30:08.240 we talked about. Oh, absolutely. The obstacles 00:30:08.240 --> 00:30:11.279 were just, as we said, formidable. She was a 00:30:11.279 --> 00:30:14.140 woman in a deeply male -dominated field. She 00:30:14.140 --> 00:30:15.920 was working in a small country, scientifically 00:30:15.920 --> 00:30:19.380 isolated, far from the big, powerful synchrotrons 00:30:19.380 --> 00:30:21.960 in Europe and the U .S. And she was working on 00:30:21.960 --> 00:30:24.200 a problem that literally everyone who mattered 00:30:24.200 --> 00:30:26.599 said was impossible. She had every single excuse 00:30:26.599 --> 00:30:29.200 to quit. Any rational person would have quit. 00:30:29.660 --> 00:30:32.039 But she didn't. She just froze the problem until 00:30:32.039 --> 00:30:33.940 it stopped moving and she could finally solve 00:30:33.940 --> 00:30:35.960 it. You know, it makes me look at the world, 00:30:36.039 --> 00:30:39.440 at my own body, so differently. I just keep thinking 00:30:39.440 --> 00:30:42.019 about that ribosomal tunnel. Right now, as we're 00:30:42.019 --> 00:30:44.440 speaking, in every single one of the trillions 00:30:44.440 --> 00:30:47.559 of cells in my body, there are millions of these 00:30:47.559 --> 00:30:50.140 little machines just humming along, reading the 00:30:50.140 --> 00:30:52.640 tape, knitting proteins, pushing them out through 00:30:52.640 --> 00:30:55.380 that little tunnel. It's a constant, silent symphony 00:30:55.380 --> 00:30:57.440 happening in the dark. And for three billion 00:30:57.440 --> 00:31:01.730 years, It was completely in the dark until A 00:31:01.730 --> 00:31:03.750 .D. Yonath finally figured out how to turn on 00:31:03.750 --> 00:31:05.410 the light. That's a beautiful way to put it. 00:31:05.529 --> 00:31:07.329 So here's the thought I want to leave our listeners 00:31:07.329 --> 00:31:10.769 with. A .D. Yonath looked at the ribosome, which 00:31:10.769 --> 00:31:13.430 was the impossible structure of her day, and 00:31:13.430 --> 00:31:16.210 she invented a new way to see it using cryotechnology. 00:31:17.630 --> 00:31:21.349 My question is, what is the next ribosome? What 00:31:21.349 --> 00:31:23.670 do you mean by that? I mean, what is the enormous, 00:31:23.710 --> 00:31:26.950 complex, messy biological structure or process 00:31:26.950 --> 00:31:29.230 that we are all ignoring right now because it's 00:31:29.230 --> 00:31:31.309 just considered too hard? What's the thing that 00:31:31.309 --> 00:31:33.329 the scientific community is telling young, stubborn 00:31:33.329 --> 00:31:35.910 scientists, don't bother with that, you'll fail? 00:31:36.450 --> 00:31:39.329 The physical basis of consciousness in the brain, 00:31:39.369 --> 00:31:41.849 maybe. The actual structures that hold a memory. 00:31:42.130 --> 00:31:45.329 Or the precise, tangled mechanisms of aging. 00:31:45.630 --> 00:31:48.049 The impossible is only impossible until someone 00:31:48.049 --> 00:31:50.690 stubborn enough comes along and invents a new 00:31:50.690 --> 00:31:53.390 kind of lens. Or a new kind of freezer. A .D. 00:31:53.390 --> 00:31:57.069 Yonath cracked the code of life's factory. Who 00:31:57.069 --> 00:31:59.170 is sitting in a classroom somewhere right now, 00:31:59.329 --> 00:32:01.869 maybe struggling to pay their tuition, who's 00:32:01.869 --> 00:32:04.630 dreaming of the next great code to crack. I can't 00:32:04.630 --> 00:32:06.769 wait to find out. Thank you for listening to 00:32:06.769 --> 00:32:09.089 this deep dive into the incredible life and science 00:32:09.089 --> 00:32:12.069 of A .D. Yonath. It's a powerful reminder that 00:32:12.069 --> 00:32:14.730 sometimes the biggest discoveries really do come 00:32:14.730 --> 00:32:16.829 from the smallest crystals. And from the most 00:32:16.829 --> 00:32:18.970 persistent minds. We'll see you on the next one. 00:32:19.069 --> 00:32:19.930 Keep exploring.