WEBVTT - AIDS is Solvable 0:00:15.076 --> 0:00:22.436 Bushkin. I'm Mave Higgins, and this is Solvable Interviews with 0:00:22.476 --> 0:00:25.796 the world's most innovative thinkers who are working to solve 0:00:25.836 --> 0:00:30.556 the world's biggest problems. Now, if this program we're airing 0:00:30.676 --> 0:00:33.476 in the early nineteen eighties and I told you that 0:00:33.516 --> 0:00:36.636 the problem of how to treat those with HIV could 0:00:36.676 --> 0:00:39.516 be solved, you laugh in my face. You might even 0:00:39.556 --> 0:00:42.476 call me a quack. Now that would be mean, because 0:00:42.556 --> 0:00:46.596 I would be a baby. But remember back then, HIV 0:00:46.916 --> 0:00:50.436 and AIDS were a terrifying epidemic, and one of the 0:00:50.436 --> 0:00:54.836 worst things was that people didn't recognize anything familiar about 0:00:54.916 --> 0:00:58.556 this new communicable disease that was laying waste to so 0:00:58.596 --> 0:01:03.276 many different groups around the world. But discovering the secrets 0:01:03.316 --> 0:01:07.676 of HIV AIDS and devising treatments for it did turn 0:01:07.756 --> 0:01:11.636 out to be solvable. For this episode, Malcolm Gladwell spoke 0:01:11.676 --> 0:01:14.876 to a man whose work was crucial to making that possible. 0:01:15.316 --> 0:01:18.836 He's one of the most influential figures in twentieth century science. 0:01:19.956 --> 0:01:22.916 My name is David Baltimore. I am a professor at 0:01:22.916 --> 0:01:28.036 the California Institute of Technology, known fondly as Caltech, and 0:01:28.716 --> 0:01:33.236 I early on in my career figured out that viruses, 0:01:33.436 --> 0:01:38.916 in their desire to grow floridly, have taken advantage of 0:01:39.196 --> 0:01:42.636 all sorts of molecular tricks, and one of them was 0:01:42.676 --> 0:01:48.556 to copy RNA and DNA, which violated the central dogma 0:01:48.636 --> 0:01:53.596 of molecular biology, but set cancer research in a new direction. 0:01:54.796 --> 0:01:57.356 Now he sounds pretty cool about it, but it was 0:01:57.396 --> 0:02:00.796 for this discovery that David Baltimore was awarded the Nobel 0:02:00.876 --> 0:02:05.276 Prize in Physiology and Medicine, along with Renato Delbacco and 0:02:05.316 --> 0:02:08.756 Howard Tremin. Now remember that name. You'll hear a lot 0:02:08.796 --> 0:02:12.956 about Howard men. The work they did independently of one another, 0:02:13.356 --> 0:02:16.996 proved that what was known then as the central dogma 0:02:17.196 --> 0:02:20.476 that genetic information carried in the building blocks of life, 0:02:20.796 --> 0:02:24.916 RNA and DNA only traveled one way, from DNA to 0:02:25.396 --> 0:02:29.396 RNA to protein. They found out that was wrong, and 0:02:29.516 --> 0:02:32.556 that knowledge enabled them to solve the mystery of how 0:02:32.716 --> 0:02:37.996 viruses cause cancer. They discovered what are known as retroviruses, 0:02:38.356 --> 0:02:42.716 and these viruses turned normal cells into cancer cells permanently 0:02:42.756 --> 0:02:47.636 by altering their DNA. David Baltimore did this work decades 0:02:47.716 --> 0:02:51.316 before the AIDS epidemic, but it was this research that 0:02:51.476 --> 0:02:55.476 made the discovery and treatment of HIV possible, something he 0:02:55.556 --> 0:02:59.716 had no idea of at the time. Malcolm Gladwell actually 0:02:59.756 --> 0:03:02.676 covered Baltimore's work when he was a science journalist for 0:03:02.756 --> 0:03:06.116 The Washington Post in the early nineteen nineties, during the 0:03:06.236 --> 0:03:09.276 race for HIV and AIDS treatments that was really a 0:03:09.356 --> 0:03:13.716 matter of public desperation. One question that stayed with Malcolm 0:03:13.716 --> 0:03:17.356 from that time, how were these scientists ready to mobilize 0:03:17.396 --> 0:03:22.516 so quickly around such a new and terrifying problem. To 0:03:22.556 --> 0:03:25.196 answer that question, let's go right back to the beginning 0:03:25.236 --> 0:03:28.756 to the nineteen sixties when Baltimore and other scientists were 0:03:28.756 --> 0:03:32.036 getting their start. They had no idea that their work 0:03:32.156 --> 0:03:36.116 would later help the world understand something it's so desperately 0:03:36.156 --> 0:03:39.516 needed to. They followed the scientific method and their own 0:03:39.596 --> 0:03:43.596 curiosity wherever that led, and sometimes the results put them 0:03:43.596 --> 0:03:46.876 at odds with the dogma of their own field. So 0:03:47.036 --> 0:03:49.276 let's meet the twenty three year old David Baltimore, who 0:03:49.316 --> 0:03:53.196 had become fascinated by animal viruses and took a course 0:03:53.236 --> 0:03:57.476 on them at Cold Spring Harbor Labs. Here's Malcolm's conversation 0:03:57.596 --> 0:04:00.836 with David Baltimore. I mean, I had lots of questions, 0:04:01.676 --> 0:04:05.116 but I was pretty clear that those questions were things 0:04:05.156 --> 0:04:07.956 that we're going to drive my life, and that I 0:04:08.036 --> 0:04:10.836 understood them well enough to be ready to do that. 0:04:11.596 --> 0:04:15.236 When you go to Cold Spring to study animal viruses, 0:04:15.476 --> 0:04:17.796 what viruses are you studying? And this is all mouse 0:04:17.836 --> 0:04:21.796 models or what is is? It's a lot's mouse models 0:04:21.916 --> 0:04:26.116 or cells. You could grow viruses in cells, and so 0:04:26.156 --> 0:04:29.516 those are the objects that we worked on. Polio or 0:04:29.596 --> 0:04:33.436 Polioli viruses were one part, and I end up doing 0:04:33.476 --> 0:04:37.636 my thesis at a Polioli virus. There were a class 0:04:37.636 --> 0:04:41.236 of viruses with membranes around them that brought us into 0:04:41.276 --> 0:04:45.956 membrane biology and very different sorts of considerations, very rich, 0:04:47.116 --> 0:04:50.236 and so we worked with those. Newcastle disease virus was 0:04:50.316 --> 0:04:53.396 one of those, and then there were viruses that cause cancer, 0:04:53.756 --> 0:04:58.436 and in particular the rousts are coomavirus. You are kind 0:04:58.476 --> 0:05:01.516 of self assuredness about what it is you wanted to do. 0:05:02.036 --> 0:05:03.956 How much of that is you and how much of 0:05:03.956 --> 0:05:06.556 that is a function of the fact that the field 0:05:06.596 --> 0:05:09.796 is in its infancy, and so only three year olds 0:05:09.796 --> 0:05:14.476 guesses as good as anyone's, right, Yeah, I suppose that's true. 0:05:15.396 --> 0:05:18.556 It would be different if you were entering an incredibly 0:05:18.556 --> 0:05:22.236 mature if yeah, all right, it probably would, yeah, because 0:05:22.836 --> 0:05:27.956 I mean I can remember weeks months when I was 0:05:27.996 --> 0:05:31.236 doing my faces at Rockefeller, in which I would come 0:05:31.276 --> 0:05:34.916 in the morning and I would work on an idea 0:05:34.996 --> 0:05:38.436 and set up experiments and read those out a couple 0:05:38.476 --> 0:05:42.796 of days later and discover something brand new. And you 0:05:42.836 --> 0:05:45.836 couldn't do that in a mature field of science because 0:05:45.836 --> 0:05:48.756 other people would have done it before you. But nobody 0:05:48.756 --> 0:05:53.676 had done these sorts of things. Ralph suckomavirus enters back 0:05:53.716 --> 0:05:57.156 into our story. Yeah, some years into the future. So 0:05:57.956 --> 0:06:01.356 I'm curious about this. As a non scientist, you encounter 0:06:01.476 --> 0:06:04.716 this virus early on in your career. In retrospect, you 0:06:04.796 --> 0:06:08.876 realize my phrasing this correctly. In retrospect, you realize you 0:06:08.956 --> 0:06:12.076 never really understood it, or you only saw a portion 0:06:12.116 --> 0:06:14.996 of it, or how would you describe your primitive understanding 0:06:15.036 --> 0:06:20.756 of that virus in retrospect. I was not interested in 0:06:20.836 --> 0:06:25.596 it as an experimental object. First of it was a 0:06:25.596 --> 0:06:28.076 hard virus to work with. Why was it hard? It 0:06:28.116 --> 0:06:30.556 didn't grow very well, It didn't you didn't get it 0:06:30.716 --> 0:06:35.476 much material, and I had not yet been captured by 0:06:35.516 --> 0:06:40.116 the problem of cancer. I just didn't think about it much, 0:06:40.956 --> 0:06:43.916 and so as part of this course, it was something 0:06:43.956 --> 0:06:47.716 that we focused attention, but I never really thought about it. 0:06:47.796 --> 0:06:54.156 Then for another ten years, almost yeah, while I worked 0:06:54.196 --> 0:06:57.396 out the sort of basic molecular biology of a variety 0:06:57.396 --> 0:07:00.556 of other viruses. And then I came back because at 0:07:00.556 --> 0:07:03.516 that point we knew the basic lifestyle of most viruses, 0:07:03.876 --> 0:07:09.796 but now the cancer inducing viruses stood out as different 0:07:09.876 --> 0:07:12.916 and hard to understand. What was different and hard to 0:07:12.996 --> 0:07:17.836 understand about them? Well, the fundamental thing was that they 0:07:17.956 --> 0:07:23.436 had RNA as their genome, and yet they were able 0:07:23.476 --> 0:07:28.436 to establish a permanent position inside the cell and run 0:07:28.516 --> 0:07:30.436 the cell. So he turned it from a normal cell 0:07:30.476 --> 0:07:33.996 to a cancer cell. There were DNA viruses that could 0:07:34.076 --> 0:07:38.756 do that, yet it was an RNA virus, and that 0:07:38.876 --> 0:07:43.236 didn't make sense. Howard had been driven by that question 0:07:44.196 --> 0:07:50.156 for ten years previously. He first formulated that question when 0:07:50.196 --> 0:07:54.396 he was graduate. During the time he's graduating from Caltech, 0:07:55.556 --> 0:07:59.436 it was a relatively easy jump for him to say 0:07:59.476 --> 0:08:03.956 the RNA must be copied into DNA, and then he 0:08:04.036 --> 0:08:12.196 spent about ten years at university was trying to find 0:08:12.236 --> 0:08:15.516 an experiment that would convince anybody else of that, and 0:08:15.556 --> 0:08:19.516 he couldn't. So Timman has sort of there's ten years 0:08:19.516 --> 0:08:23.396 in the wilderness, and he's not getting a lot of 0:08:23.476 --> 0:08:26.756 encouragement from the scientific community in those ten years. Why 0:08:27.916 --> 0:08:33.796 because the papers he's publishing are not convincing. So this 0:08:33.836 --> 0:08:38.036 is is it sub tribute to his own innate suberness, 0:08:38.196 --> 0:08:42.156 his own he convinced himself on some theoretical level that 0:08:42.636 --> 0:08:46.116 there must be something there because he was driven by 0:08:46.236 --> 0:08:53.076 that by his observation that the virus controlled the behavior 0:08:53.116 --> 0:08:57.716 of the cells. Only genes control the behavior of cells, 0:08:58.396 --> 0:09:02.476 and so the virus had to put it information in 0:09:02.516 --> 0:09:06.596 the form of genes, and DNA was the form of genes. 0:09:07.556 --> 0:09:11.276 He sort of religious he believed that therefore the information 0:09:11.436 --> 0:09:14.476 RNA had to be read to DNA. And he wasn't 0:09:14.596 --> 0:09:18.036 much of a chemist. He didn't think like a biochemist. 0:09:18.076 --> 0:09:22.356 He thought like a geneticist. So the idea that RNA 0:09:22.476 --> 0:09:27.556 could template DNA made sense to him as words, but 0:09:27.876 --> 0:09:31.876 he had never actually done an experiment that looked at that. I, 0:09:32.076 --> 0:09:35.036 on the other hand, had spent those ten years doing 0:09:35.676 --> 0:09:39.316 that form of experiment with all sorts of different biological 0:09:39.396 --> 0:09:43.156 materials and all sorts of different ways. That was my 0:09:43.236 --> 0:09:46.076 bread and butter. Yeah. So yeah, let's let's talk about 0:09:46.076 --> 0:09:49.276 your entry into this. So Don Keudy is up in 0:09:49.276 --> 0:09:53.716 Wisconsin tilting in a windmill. Yes, and David Baltibor decides 0:09:53.756 --> 0:09:59.396 to join in the windmill tilting. At what point do 0:09:59.476 --> 0:10:04.116 you does this battle attract you? I mean, I know 0:10:04.356 --> 0:10:08.396 exactly what form because I had been working on a 0:10:08.516 --> 0:10:12.996 virus called vesiculostalmatitis virus, and we had discovered that it's 0:10:13.996 --> 0:10:20.556 the complement of the sense strand of RNA. So it's 0:10:20.556 --> 0:10:23.916 a senseless strand that acts solely as a template to 0:10:24.036 --> 0:10:29.516 make sense strands. And if you think about that, a 0:10:29.596 --> 0:10:33.556 virus like that can't just go into a cell and 0:10:33.716 --> 0:10:37.676 take over the cell because it has to copy it's 0:10:37.796 --> 0:10:40.956 RNA into messenger RNA. And the only way it can 0:10:40.996 --> 0:10:43.436 do that is if either the cell has an enzyme 0:10:43.476 --> 0:10:45.876 to do that, and we had looked for such a 0:10:46.316 --> 0:10:49.796 enzyme could never find one, or if the enzyme was 0:10:49.836 --> 0:10:54.276 in the virus particle. So I had looked for it 0:10:54.356 --> 0:10:58.716 in the virus particle and found that the virus particle 0:10:58.796 --> 0:11:03.356 had an RNA dependent RNA plumb race that copied the 0:11:04.316 --> 0:11:08.076 senseless strand into a sense strand, and that's clearly how 0:11:08.156 --> 0:11:11.236 infection got started. It and suddenly I opened up a 0:11:11.236 --> 0:11:14.996 whole field of negative strand viruses. So now it became 0:11:15.236 --> 0:11:19.716 trivial to say, well, you know, maybe Howard has something. 0:11:20.276 --> 0:11:23.676 Let's have a look at the virus particles of RN 0:11:23.756 --> 0:11:28.156 tumb virus. They might have an enzyme that copies are 0:11:28.236 --> 0:11:30.156 an agency in it. Oh, I see. Once you had 0:11:30.196 --> 0:11:33.796 made the insight that these viruses are carrying around their 0:11:33.836 --> 0:11:37.836 own photocopiers or whatever it is, right, they have a 0:11:37.836 --> 0:11:40.716 little a little in house xerox, you're like, oh, let's 0:11:40.756 --> 0:11:45.156 just look for the maybe these are everywhere versions of them. 0:11:45.196 --> 0:11:48.036 The minute you find the enzyme and the one you're 0:11:48.076 --> 0:11:50.476 working on, is it instant that you think about what 0:11:50.516 --> 0:11:52.956 Howard's doing or is it something you pops into your 0:11:52.996 --> 0:11:54.756 head six months later. I'm just so curious about that 0:11:54.836 --> 0:11:59.836 kind of what does that insight mean? I think it 0:11:59.876 --> 0:12:04.076 wasn't very long. We did one other thing first, which 0:12:04.156 --> 0:12:07.076 is we wanted to extend it to other viruses that 0:12:07.356 --> 0:12:10.836 looked the same in the electron microscope, and we found 0:12:10.956 --> 0:12:15.076 a number of other negative strands viruses right away. And 0:12:15.116 --> 0:12:18.196 then I said, where else can we carry this idea to? 0:12:18.316 --> 0:12:21.556 And I said, well, how about RNA tumor viruses? How 0:12:21.556 --> 0:12:24.716 hard was it to find this particular enzyme? Is that? 0:12:25.036 --> 0:12:29.316 Is it trivial? Oh? Really, it's really the two two 0:12:29.356 --> 0:12:33.996 days of experiments two days. So it's just the idea 0:12:34.116 --> 0:12:36.916 of knowing where to look and what to look for 0:12:37.076 --> 0:12:40.756 and what to look for. Right, naive and weird question. 0:12:41.316 --> 0:12:45.396 Do you know what you've done at the time? Yeah, 0:12:45.436 --> 0:12:48.956 I knew what we had done in terms of cancer. 0:12:49.556 --> 0:12:52.636 It was clear that we had broken over cancer research. 0:12:53.556 --> 0:12:58.796 I didn't know what else we'd done. HIV hadn't been discovered. 0:12:58.796 --> 0:13:02.916 I didn't know we had set up the understanding of HIV. 0:13:03.676 --> 0:13:08.436 I didn't know that the genome of humans and all 0:13:08.556 --> 0:13:13.116 organisms has lots of reverse transcribed DNA in It comes 0:13:13.116 --> 0:13:16.516 from various sources. So it was much richer and more 0:13:16.516 --> 0:13:22.716 complex than I could say with any assurance except for 0:13:22.796 --> 0:13:26.716 the implications for cancer. Yeah, we're gonna talk a little 0:13:26.716 --> 0:13:29.876 bit about HIV for a moment, undo a kind of 0:13:29.916 --> 0:13:35.996 alternate history. If HIV arrives as a force ten years earlier, 0:13:36.156 --> 0:13:41.876 in sixty seven, not seventy seven, what happens scientifically medically disaster. 0:13:42.756 --> 0:13:46.676 The worst thing that can happen, and it was proved 0:13:46.756 --> 0:13:51.876 in the HIV epidemic, is not to know what's causing 0:13:51.876 --> 0:13:57.996 a disease, because that gives liberty to fantasy, and one 0:13:58.036 --> 0:14:01.396 person's fantasy is as good as another's. So you don't 0:14:01.396 --> 0:14:05.036 know who to believe. The public doesn't know what to believe. 0:14:06.236 --> 0:14:08.436 You don't know how it's spread, You don't know if 0:14:08.436 --> 0:14:13.956 it is in factious. The early days of the HIV epidemic, 0:14:14.196 --> 0:14:18.836 there are all sorts of theories about homosexual sex poppers, 0:14:19.156 --> 0:14:22.596 drugs people were taking. Until you knew it was a virus, 0:14:23.196 --> 0:14:25.756 you didn't know how to intervene. You didn't know what 0:14:25.796 --> 0:14:30.356 to do to protect yourself. So HIV is more than 0:14:31.196 --> 0:14:34.676 a virus. It's a retrovirus, and it's operating by the 0:14:34.756 --> 0:14:38.916 very principles that you intem and uncovered. But absent that knowledge, 0:14:39.036 --> 0:14:40.876 we could know it was infectious and know it was 0:14:40.916 --> 0:14:43.676 a virus, but not be able to We couldn't find it. 0:14:43.716 --> 0:14:46.596 Couldn't find it. You can't find it unless you know 0:14:46.676 --> 0:14:50.236 it's this particular class of right. It was the search 0:14:50.476 --> 0:14:56.956 for reverse transcripts in the virus particles that opened up 0:14:56.956 --> 0:14:59.356 the knowledge that it was a virus that was causing 0:14:59.356 --> 0:15:05.436 the disease. Yeah. Yeah. And then secondarily, you can't even 0:15:05.516 --> 0:15:09.436 begin to design drugs against it because aren't am I 0:15:09.516 --> 0:15:12.476 right that the first wave of successful drugs are all 0:15:12.556 --> 0:15:16.396 those that at reversian ships. Yeah, yes, yeah, they are 0:15:16.396 --> 0:15:21.676 attacking this very vulnerability. They are nucleodide analogs, so they 0:15:21.876 --> 0:15:26.196 look like pieces of RNA. Describe in the most DNA 0:15:26.356 --> 0:15:29.716 I mean, yes, describe the mechanism of that first wave 0:15:29.756 --> 0:15:34.756 of successful anti HIV drugs. The way that you copy 0:15:35.276 --> 0:15:40.516 RNA into DNA is by copying one nucleotide at a 0:15:40.636 --> 0:15:45.716 time into its compliment by the complimentary rules that had 0:15:45.796 --> 0:15:48.676 been laid down by Watson and Crick that A pairs 0:15:48.716 --> 0:15:53.476 would t and g pears would see. What these drugs 0:15:53.516 --> 0:15:59.636 were were analogs of the ATGC that fit into the 0:15:59.716 --> 0:16:04.796 slot where the copying went on, but then couldn't be 0:16:04.836 --> 0:16:09.756 extended further, so they terminated the growth of the DNAH 0:16:10.956 --> 0:16:13.716 and they are that's what they're called chain terminators. And 0:16:13.836 --> 0:16:19.116 the theoretical basis for that entire operation is the understanding 0:16:19.116 --> 0:16:22.476 that this is a virus that is operating through the 0:16:22.516 --> 0:16:26.076 principles of a verse right. If you didn't know that, 0:16:26.516 --> 0:16:29.356 if you didn't ask that question, you wouldn't have found 0:16:29.356 --> 0:16:31.676 the virus and we would have been in the wilderness. 0:16:32.516 --> 0:16:36.876 So if it had come about ten years earlier before 0:16:37.036 --> 0:16:40.796 we had the reverse transcript tase, it would have been 0:16:40.836 --> 0:16:43.436 a lot longer before we understood that it was a virus. 0:16:44.036 --> 0:16:46.636 If I don't know how long it would have been. 0:16:47.036 --> 0:16:50.236 I'm wondering whether once the sort of dust settles on 0:16:50.276 --> 0:16:53.316 the discovery of verse transcript tase, is there a moment 0:16:53.316 --> 0:16:56.676 when your mind wanders and you start to think about 0:16:56.716 --> 0:16:59.196 all of the lung Like I know you said immediately 0:16:59.236 --> 0:17:00.596 it was clear it was going to have an impact 0:17:00.636 --> 0:17:03.756 on cancer, But did it ever for example, did it 0:17:03.756 --> 0:17:06.516 ever out of the blue occurred to you that wow, 0:17:07.076 --> 0:17:11.076 what if we did have a consequential virus that came 0:17:11.076 --> 0:17:14.436 along that operated, that was a retrovirus. Now we're in 0:17:14.476 --> 0:17:16.036 a much stronger I mean, I wanted to do you 0:17:16.076 --> 0:17:18.316 ever gain out any of these scenarios in your mind? 0:17:19.116 --> 0:17:23.636 Not a whole lot, because because we had enough to 0:17:23.636 --> 0:17:27.396 think about it now, I then became passionately interesting in 0:17:27.596 --> 0:17:32.476 how you copy on RNA into a DNA. And when 0:17:32.516 --> 0:17:36.196 I say, how there are all sorts of details of 0:17:36.276 --> 0:17:40.956 that process that are just fascinating molecular biology. And so 0:17:41.596 --> 0:17:45.316 there was an area in my lab which focused on that. 0:17:46.436 --> 0:17:51.196 The other thing we focused on was retroviruses and their 0:17:51.236 --> 0:17:55.476 ability to cause cancer because we had opened up a 0:17:55.636 --> 0:17:58.756 field and I wanted to be part of that field, 0:17:59.516 --> 0:18:03.516 and so I went out on a hunt for a 0:18:03.596 --> 0:18:07.836 mouse virus that was as good as routs circumavirus as 0:18:07.916 --> 0:18:10.716 an object of study, but you could do it in 0:18:10.756 --> 0:18:14.156 the context of mass genetics, and so you really could 0:18:14.676 --> 0:18:20.716 take advantage of the whole history of mass biology. And 0:18:20.876 --> 0:18:25.116 I found one and which was it's called Abelson mirroring 0:18:25.196 --> 0:18:30.036 leukemia virus, and it was the secret to understanding chronic 0:18:30.076 --> 0:18:33.356 myologist leukemia in the end, I mean, because it turned 0:18:33.356 --> 0:18:37.116 out to be a virus that used an enzyme that 0:18:37.756 --> 0:18:40.876 was part of the very serious human disease. But I 0:18:40.876 --> 0:18:42.596 didn't know that at the time. I mean, it was 0:18:42.676 --> 0:18:45.596 just a model that fit what I wanted to do 0:18:45.636 --> 0:18:49.716 in a lab, So I didn't think a whole lot 0:18:49.756 --> 0:18:53.956 about where else there might be viruses like this, and 0:18:54.276 --> 0:18:57.316 there were so many other people doing that right away. 0:18:57.756 --> 0:19:00.636 Coming back to HIV for a moment, when it comes 0:19:00.676 --> 0:19:04.556 time to construct these anti virals for HIV. You're obviously 0:19:04.556 --> 0:19:09.556 borrowing the central scientific insight. Here are they also bill 0:19:09.636 --> 0:19:13.196 borrowing from all of this subsequent filling in all the 0:19:13.196 --> 0:19:15.676 gaps work. I mean, if you were saying you then 0:19:15.756 --> 0:19:19.676 got really interested in how this process of yeah, they 0:19:19.756 --> 0:19:22.476 are they taking at work and using that to help 0:19:22.516 --> 0:19:29.796 construct construct drugs. Yes, yeah, yeah, yeah. For instance, the integrace. 0:19:30.276 --> 0:19:34.276 I mean, we didn't discover integrace, but working out the 0:19:34.316 --> 0:19:38.636 details of reverse transcription, ultimately you come to something which 0:19:38.636 --> 0:19:41.836 has to go into the nucleus and associate itself with 0:19:41.916 --> 0:19:44.876 a DNA and the nucleus, and that was an integrace. 0:19:45.236 --> 0:19:48.996 So integrace inhibitors turn out to be the very best drugs, 0:19:49.956 --> 0:19:53.196 and there were a number of others. Protease is a 0:19:53.236 --> 0:19:57.796 proteas that's very important, cutting up proteins into white sized pieces, 0:19:59.076 --> 0:20:02.036 and if you inhibit that, you can prevent the virus 0:20:02.036 --> 0:20:05.316 from growing. And so there are protease inhibitors. So yeah, 0:20:05.316 --> 0:20:09.316 every aspect of the virus that we've ever studied then 0:20:09.476 --> 0:20:13.676 lends itself to the development of drug At the time 0:20:13.716 --> 0:20:17.036 you're doing all this work, how large is your lab? Oh, 0:20:17.196 --> 0:20:22.236 it's about five or six people, it's you, a couple 0:20:22.236 --> 0:20:27.916 of students, a couple of post docs. It's tiny, small. 0:20:28.236 --> 0:20:31.356 I mean I had only just moved to MT in 0:20:31.436 --> 0:20:36.196 sixty eight. Yeah, so I didn't yet have a sort 0:20:36.196 --> 0:20:38.756 of pipeline of people to me into the lab. What 0:20:38.916 --> 0:20:40.956 grants so you have do you have at that moment? 0:20:41.516 --> 0:20:46.356 I have grants from NIH, largely to do work on 0:20:47.196 --> 0:20:52.516 mangovirus and poliovirus. I don't think I got any grants. 0:20:52.996 --> 0:20:55.196 I certainly didn't get a grant to work on Darna 0:20:55.236 --> 0:20:59.196 toumber viruses. And we did the negative strand virus work 0:20:59.236 --> 0:21:02.636 without grants. We just use the money we had from 0:21:02.756 --> 0:21:07.076 other sources. But how large are those grants this is 0:21:07.116 --> 0:21:12.036 late sixties. Oh, they're probably one hundred thousand dollars. Was 0:21:12.076 --> 0:21:15.636 a lot of money in those days. I don't remember, 0:21:16.596 --> 0:21:18.996 do you when you said when you made that an observation, 0:21:19.036 --> 0:21:22.676 and you're like, oh, maybe that is explains what tem 0:21:22.676 --> 0:21:25.556 And has been puzzling over. I love the way in 0:21:25.596 --> 0:21:29.636 which so the two of you contribute beautifully to this, 0:21:29.836 --> 0:21:33.236 to the success of this problem, coming from different directions. 0:21:33.596 --> 0:21:37.676 If tim And hasn't been puzzling over it, was that 0:21:37.756 --> 0:21:39.276 thought still a bit in the back of your mind. 0:21:41.076 --> 0:21:46.236 Perhaps not if nobody had been thinking about it, would 0:21:46.316 --> 0:21:50.396 I have come to it. I don't know. It's a 0:21:51.116 --> 0:21:55.436 very hard hypothetical too. Yeah, partly because I, as I said, 0:21:55.476 --> 0:21:58.756 I knew knew about Howard's interest in work for that 0:21:58.796 --> 0:22:02.716 whole ten year period. Yeah, I asked what was going 0:22:02.756 --> 0:22:05.956 on in virology? That was one thing going on virology. 0:22:06.476 --> 0:22:11.596 I'm curious about what has that experience taught you about 0:22:11.716 --> 0:22:16.396 the way science ought to be structured. Well, one of 0:22:16.396 --> 0:22:22.716 the most important things to me is that young people 0:22:23.636 --> 0:22:27.916 often do things that are sort of off the beaten 0:22:27.916 --> 0:22:34.516 track and can produce real change in the way we think. 0:22:35.436 --> 0:22:40.636 And so it's very important to give young people that opportunity, 0:22:40.716 --> 0:22:45.396 and that the way we've structured the educational process in science, 0:22:46.236 --> 0:22:51.276 we don't give people enough independence early enough in their 0:22:51.316 --> 0:22:55.276 careers to take full advantage of the time when I 0:22:55.316 --> 0:22:59.796 think you sort of naturally have the most creative opportunities. 0:23:00.756 --> 0:23:03.876 And so the fact that I was and I'm partly 0:23:03.956 --> 0:23:09.556 modeling that statement on my own life because I managed 0:23:09.596 --> 0:23:13.236 to get that kind of independence from very early on, 0:23:14.276 --> 0:23:16.076 partly because of the people I chose to work with, 0:23:16.876 --> 0:23:21.116 partly because I was I guess fairly aggressive about it, 0:23:22.436 --> 0:23:26.236 and so I was making my own decisions in science 0:23:26.436 --> 0:23:31.956 from the time I really started out. Most people don't 0:23:31.996 --> 0:23:36.876 get that opportunity, and most people probably can't handle it, 0:23:37.436 --> 0:23:39.396 but there are more people who can handle it than 0:23:39.796 --> 0:23:43.676 are given the opportunity. So I have, as I've gone 0:23:43.676 --> 0:23:49.076 on and built institutions, tried to build into that the 0:23:49.156 --> 0:23:53.236 opportunity for young people to get that kind of freedom 0:23:53.276 --> 0:23:57.396 as early as possible, so that they can take advantage 0:23:57.396 --> 0:24:00.356 of the time when I think they're most creative and 0:24:00.676 --> 0:24:07.436 they're also least burdened by personal responsibility. And today, when 0:24:07.476 --> 0:24:12.036 people get out of their training thirty five if they're lucky, 0:24:12.076 --> 0:24:14.116 by which time they have families, and they have also 0:24:14.196 --> 0:24:18.116 two other responsibilities. And I think that that's a shame. 0:24:18.916 --> 0:24:21.716 Does a young David Baltimore in twenty nineteen have a 0:24:21.716 --> 0:24:24.276 harder or easier time of it than a David Baltimore 0:24:24.276 --> 0:24:29.676 in nineteen fifty. I think it's harder now, but it's 0:24:29.676 --> 0:24:32.636 not impossible. One thing I set up that a lot 0:24:32.636 --> 0:24:38.436 of places have emulated is a fellows program at the 0:24:38.436 --> 0:24:42.116 White Hidden Institute, which I started, which isn't a time 0:24:42.156 --> 0:24:45.996 that people can be independent and yet not have done 0:24:45.996 --> 0:24:50.156 a post door and only the very best people are 0:24:50.196 --> 0:24:53.596 accepted in it, and it's just turned out one after 0:24:53.636 --> 0:24:57.596 another great people. Thank you very much. There's something I 0:24:57.636 --> 0:25:00.356 should tell you, because I don't think you know it. 0:25:00.916 --> 0:25:05.516 And that's actually what happened. The day after I made 0:25:05.516 --> 0:25:11.316 the discovery, Oh Nixon invaded Cambodi. You and m I 0:25:11.636 --> 0:25:15.956 went on strike and I was in the streets supporting 0:25:15.996 --> 0:25:20.756 my graduate getting out of jail, leading groups marching down 0:25:20.756 --> 0:25:25.636 the streets of Gambridge for about five days, and then 0:25:25.676 --> 0:25:27.916 I came back to the lab, thought it all out 0:25:27.956 --> 0:25:41.436 and finished the experiments. Strange world we live in. This episode, 0:25:41.476 --> 0:25:45.756 to me, really highlights how a scientists curiosity, conviction, and 0:25:45.996 --> 0:25:49.756 creativity can all combine to one day help somebody face 0:25:50.196 --> 0:25:53.636 perhaps the most devastating diagnosis they'll ever have to face. 0:25:54.396 --> 0:25:56.836 And also it made me think about how giving young 0:25:56.916 --> 0:25:59.796 sciences a chance to make their own choices and to 0:25:59.956 --> 0:26:02.596 be creative, even when they're early on in their careers, 0:26:02.996 --> 0:26:07.316 when expertise and experience seems to be extremely important, that's 0:26:07.356 --> 0:26:11.156 good too. And as of course, as David Baltimore pointed out, 0:26:11.156 --> 0:26:13.956 it takes more than one person's work to come up 0:26:13.996 --> 0:26:18.156 with actual treatments that end up saving lives. The intellectual 0:26:18.236 --> 0:26:22.196 generosity he's shown throughout his career and now into his 0:26:22.276 --> 0:26:25.356 teaching life is exciting to think about, and it gives 0:26:25.396 --> 0:26:28.756 me hope that many more problems we once saw as 0:26:28.756 --> 0:26:32.676 the end of the road are in fact solvable now. 0:26:32.716 --> 0:26:36.116 If you're interested. Malcolm Gladwell has actually dedicated an episode 0:26:36.156 --> 0:26:39.836 of his podcast Revisionist History to the story of the 0:26:39.956 --> 0:26:44.356 search for retroviruses, and it features David Baltimore. It's called 0:26:44.436 --> 0:26:47.356 The Obscure Virus Club. I hope you'll go and listen. 0:26:49.676 --> 0:26:54.436 Solvable is a collaboration between Pushkin Industries and the Rockefeller Foundation, 0:26:54.556 --> 0:26:58.596 with production by Laura Hyde, Hester Kant, Laura Sheeter, and 0:26:58.676 --> 0:27:02.556 Ruth Barnes from Chalk and Blade. Pushkin's executive producer is 0:27:02.636 --> 0:27:07.596 Neil LaBelle. Research by Sheer, Vincent, engineering by Jason Gambrel 0:27:07.676 --> 0:27:12.116 and the great folks at SI Studios. Original music composed 0:27:12.116 --> 0:27:16.276 by Pascal Wise and special thanks to Maggie Taylor, Heather Fine, 0:27:16.476 --> 0:27:21.276 Julia Barton, Carli Mgliori, Jacob Weisberg, and Malcolm Gladwell. You 0:27:21.316 --> 0:27:25.396 can learn more about solving today's biggest problems at Rockefeller 0:27:25.476 --> 0:27:30.196 Foundation dot org slash solvable. I'm Mave Higgins. Now go 0:27:30.476 --> 0:27:30.876 solve it.