1 00:00:15,076 --> 00:00:22,436 Speaker 1: Bushkin. I'm Mave Higgins, and this is Solvable Interviews with 2 00:00:22,476 --> 00:00:25,796 Speaker 1: the world's most innovative thinkers who are working to solve 3 00:00:25,836 --> 00:00:30,556 Speaker 1: the world's biggest problems. Now, if this program we're airing 4 00:00:30,676 --> 00:00:33,476 Speaker 1: in the early nineteen eighties and I told you that 5 00:00:33,516 --> 00:00:36,636 Speaker 1: the problem of how to treat those with HIV could 6 00:00:36,676 --> 00:00:39,516 Speaker 1: be solved, you laugh in my face. You might even 7 00:00:39,556 --> 00:00:42,476 Speaker 1: call me a quack. Now that would be mean, because 8 00:00:42,556 --> 00:00:46,596 Speaker 1: I would be a baby. But remember back then, HIV 9 00:00:46,916 --> 00:00:50,436 Speaker 1: and AIDS were a terrifying epidemic, and one of the 10 00:00:50,436 --> 00:00:54,836 Speaker 1: worst things was that people didn't recognize anything familiar about 11 00:00:54,916 --> 00:00:58,556 Speaker 1: this new communicable disease that was laying waste to so 12 00:00:58,596 --> 00:01:03,276 Speaker 1: many different groups around the world. But discovering the secrets 13 00:01:03,316 --> 00:01:07,676 Speaker 1: of HIV AIDS and devising treatments for it did turn 14 00:01:07,756 --> 00:01:11,636 Speaker 1: out to be solvable. For this episode, Malcolm Gladwell spoke 15 00:01:11,676 --> 00:01:14,876 Speaker 1: to a man whose work was crucial to making that possible. 16 00:01:15,316 --> 00:01:18,836 Speaker 1: He's one of the most influential figures in twentieth century science. 17 00:01:19,956 --> 00:01:22,916 Speaker 1: My name is David Baltimore. I am a professor at 18 00:01:22,916 --> 00:01:28,036 Speaker 1: the California Institute of Technology, known fondly as Caltech, and 19 00:01:28,716 --> 00:01:33,236 Speaker 1: I early on in my career figured out that viruses, 20 00:01:33,436 --> 00:01:38,916 Speaker 1: in their desire to grow floridly, have taken advantage of 21 00:01:39,196 --> 00:01:42,636 Speaker 1: all sorts of molecular tricks, and one of them was 22 00:01:42,676 --> 00:01:48,556 Speaker 1: to copy RNA and DNA, which violated the central dogma 23 00:01:48,636 --> 00:01:53,596 Speaker 1: of molecular biology, but set cancer research in a new direction. 24 00:01:54,796 --> 00:01:57,356 Speaker 1: Now he sounds pretty cool about it, but it was 25 00:01:57,396 --> 00:02:00,796 Speaker 1: for this discovery that David Baltimore was awarded the Nobel 26 00:02:00,876 --> 00:02:05,276 Speaker 1: Prize in Physiology and Medicine, along with Renato Delbacco and 27 00:02:05,316 --> 00:02:08,756 Speaker 1: Howard Tremin. Now remember that name. You'll hear a lot 28 00:02:08,796 --> 00:02:12,956 Speaker 1: about Howard men. The work they did independently of one another, 29 00:02:13,356 --> 00:02:16,996 Speaker 1: proved that what was known then as the central dogma 30 00:02:17,196 --> 00:02:20,476 Speaker 1: that genetic information carried in the building blocks of life, 31 00:02:20,796 --> 00:02:24,916 Speaker 1: RNA and DNA only traveled one way, from DNA to 32 00:02:25,396 --> 00:02:29,396 Speaker 1: RNA to protein. They found out that was wrong, and 33 00:02:29,516 --> 00:02:32,556 Speaker 1: that knowledge enabled them to solve the mystery of how 34 00:02:32,716 --> 00:02:37,996 Speaker 1: viruses cause cancer. They discovered what are known as retroviruses, 35 00:02:38,356 --> 00:02:42,716 Speaker 1: and these viruses turned normal cells into cancer cells permanently 36 00:02:42,756 --> 00:02:47,636 Speaker 1: by altering their DNA. David Baltimore did this work decades 37 00:02:47,716 --> 00:02:51,316 Speaker 1: before the AIDS epidemic, but it was this research that 38 00:02:51,476 --> 00:02:55,476 Speaker 1: made the discovery and treatment of HIV possible, something he 39 00:02:55,556 --> 00:02:59,716 Speaker 1: had no idea of at the time. Malcolm Gladwell actually 40 00:02:59,756 --> 00:03:02,676 Speaker 1: covered Baltimore's work when he was a science journalist for 41 00:03:02,756 --> 00:03:06,116 Speaker 1: The Washington Post in the early nineteen nineties, during the 42 00:03:06,236 --> 00:03:09,276 Speaker 1: race for HIV and AIDS treatments that was really a 43 00:03:09,356 --> 00:03:13,716 Speaker 1: matter of public desperation. One question that stayed with Malcolm 44 00:03:13,716 --> 00:03:17,356 Speaker 1: from that time, how were these scientists ready to mobilize 45 00:03:17,396 --> 00:03:22,516 Speaker 1: so quickly around such a new and terrifying problem. To 46 00:03:22,556 --> 00:03:25,196 Speaker 1: answer that question, let's go right back to the beginning 47 00:03:25,236 --> 00:03:28,756 Speaker 1: to the nineteen sixties when Baltimore and other scientists were 48 00:03:28,756 --> 00:03:32,036 Speaker 1: getting their start. They had no idea that their work 49 00:03:32,156 --> 00:03:36,116 Speaker 1: would later help the world understand something it's so desperately 50 00:03:36,156 --> 00:03:39,516 Speaker 1: needed to. They followed the scientific method and their own 51 00:03:39,596 --> 00:03:43,596 Speaker 1: curiosity wherever that led, and sometimes the results put them 52 00:03:43,596 --> 00:03:46,876 Speaker 1: at odds with the dogma of their own field. So 53 00:03:47,036 --> 00:03:49,276 Speaker 1: let's meet the twenty three year old David Baltimore, who 54 00:03:49,316 --> 00:03:53,196 Speaker 1: had become fascinated by animal viruses and took a course 55 00:03:53,236 --> 00:03:57,476 Speaker 1: on them at Cold Spring Harbor Labs. Here's Malcolm's conversation 56 00:03:57,596 --> 00:04:00,836 Speaker 1: with David Baltimore. I mean, I had lots of questions, 57 00:04:01,676 --> 00:04:05,116 Speaker 1: but I was pretty clear that those questions were things 58 00:04:05,156 --> 00:04:07,956 Speaker 1: that we're going to drive my life, and that I 59 00:04:08,036 --> 00:04:10,836 Speaker 1: understood them well enough to be ready to do that. 60 00:04:11,596 --> 00:04:15,236 Speaker 1: When you go to Cold Spring to study animal viruses, 61 00:04:15,476 --> 00:04:17,796 Speaker 1: what viruses are you studying? And this is all mouse 62 00:04:17,836 --> 00:04:21,796 Speaker 1: models or what is is? It's a lot's mouse models 63 00:04:21,916 --> 00:04:26,116 Speaker 1: or cells. You could grow viruses in cells, and so 64 00:04:26,156 --> 00:04:29,516 Speaker 1: those are the objects that we worked on. Polio or 65 00:04:29,596 --> 00:04:33,436 Speaker 1: Polioli viruses were one part, and I end up doing 66 00:04:33,476 --> 00:04:37,636 Speaker 1: my thesis at a Polioli virus. There were a class 67 00:04:37,636 --> 00:04:41,236 Speaker 1: of viruses with membranes around them that brought us into 68 00:04:41,276 --> 00:04:45,956 Speaker 1: membrane biology and very different sorts of considerations, very rich, 69 00:04:47,116 --> 00:04:50,236 Speaker 1: and so we worked with those. Newcastle disease virus was 70 00:04:50,316 --> 00:04:53,396 Speaker 1: one of those, and then there were viruses that cause cancer, 71 00:04:53,756 --> 00:04:58,436 Speaker 1: and in particular the rousts are coomavirus. You are kind 72 00:04:58,476 --> 00:05:01,516 Speaker 1: of self assuredness about what it is you wanted to do. 73 00:05:02,036 --> 00:05:03,956 Speaker 1: How much of that is you and how much of 74 00:05:03,956 --> 00:05:06,556 Speaker 1: that is a function of the fact that the field 75 00:05:06,596 --> 00:05:09,796 Speaker 1: is in its infancy, and so only three year olds 76 00:05:09,796 --> 00:05:14,476 Speaker 1: guesses as good as anyone's, right, Yeah, I suppose that's true. 77 00:05:15,396 --> 00:05:18,556 Speaker 1: It would be different if you were entering an incredibly 78 00:05:18,556 --> 00:05:22,236 Speaker 1: mature if yeah, all right, it probably would, yeah, because 79 00:05:22,836 --> 00:05:27,956 Speaker 1: I mean I can remember weeks months when I was 80 00:05:27,996 --> 00:05:31,236 Speaker 1: doing my faces at Rockefeller, in which I would come 81 00:05:31,276 --> 00:05:34,916 Speaker 1: in the morning and I would work on an idea 82 00:05:34,996 --> 00:05:38,436 Speaker 1: and set up experiments and read those out a couple 83 00:05:38,476 --> 00:05:42,796 Speaker 1: of days later and discover something brand new. And you 84 00:05:42,836 --> 00:05:45,836 Speaker 1: couldn't do that in a mature field of science because 85 00:05:45,836 --> 00:05:48,756 Speaker 1: other people would have done it before you. But nobody 86 00:05:48,756 --> 00:05:53,676 Speaker 1: had done these sorts of things. Ralph suckomavirus enters back 87 00:05:53,716 --> 00:05:57,156 Speaker 1: into our story. Yeah, some years into the future. So 88 00:05:57,956 --> 00:06:01,356 Speaker 1: I'm curious about this. As a non scientist, you encounter 89 00:06:01,476 --> 00:06:04,716 Speaker 1: this virus early on in your career. In retrospect, you 90 00:06:04,796 --> 00:06:08,876 Speaker 1: realize my phrasing this correctly. In retrospect, you realize you 91 00:06:08,956 --> 00:06:12,076 Speaker 1: never really understood it, or you only saw a portion 92 00:06:12,116 --> 00:06:14,996 Speaker 1: of it, or how would you describe your primitive understanding 93 00:06:15,036 --> 00:06:20,756 Speaker 1: of that virus in retrospect. I was not interested in 94 00:06:20,836 --> 00:06:25,596 Speaker 1: it as an experimental object. First of it was a 95 00:06:25,596 --> 00:06:28,076 Speaker 1: hard virus to work with. Why was it hard? It 96 00:06:28,116 --> 00:06:30,556 Speaker 1: didn't grow very well, It didn't you didn't get it 97 00:06:30,716 --> 00:06:35,476 Speaker 1: much material, and I had not yet been captured by 98 00:06:35,516 --> 00:06:40,116 Speaker 1: the problem of cancer. I just didn't think about it much, 99 00:06:40,956 --> 00:06:43,916 Speaker 1: and so as part of this course, it was something 100 00:06:43,956 --> 00:06:47,716 Speaker 1: that we focused attention, but I never really thought about it. 101 00:06:47,796 --> 00:06:54,156 Speaker 1: Then for another ten years, almost yeah, while I worked 102 00:06:54,196 --> 00:06:57,396 Speaker 1: out the sort of basic molecular biology of a variety 103 00:06:57,396 --> 00:07:00,556 Speaker 1: of other viruses. And then I came back because at 104 00:07:00,556 --> 00:07:03,516 Speaker 1: that point we knew the basic lifestyle of most viruses, 105 00:07:03,876 --> 00:07:09,796 Speaker 1: but now the cancer inducing viruses stood out as different 106 00:07:09,876 --> 00:07:12,916 Speaker 1: and hard to understand. What was different and hard to 107 00:07:12,996 --> 00:07:17,836 Speaker 1: understand about them? Well, the fundamental thing was that they 108 00:07:17,956 --> 00:07:23,436 Speaker 1: had RNA as their genome, and yet they were able 109 00:07:23,476 --> 00:07:28,436 Speaker 1: to establish a permanent position inside the cell and run 110 00:07:28,516 --> 00:07:30,436 Speaker 1: the cell. So he turned it from a normal cell 111 00:07:30,476 --> 00:07:33,996 Speaker 1: to a cancer cell. There were DNA viruses that could 112 00:07:34,076 --> 00:07:38,756 Speaker 1: do that, yet it was an RNA virus, and that 113 00:07:38,876 --> 00:07:43,236 Speaker 1: didn't make sense. Howard had been driven by that question 114 00:07:44,196 --> 00:07:50,156 Speaker 1: for ten years previously. He first formulated that question when 115 00:07:50,196 --> 00:07:54,396 Speaker 1: he was graduate. During the time he's graduating from Caltech, 116 00:07:55,556 --> 00:07:59,436 Speaker 1: it was a relatively easy jump for him to say 117 00:07:59,476 --> 00:08:03,956 Speaker 1: the RNA must be copied into DNA, and then he 118 00:08:04,036 --> 00:08:12,196 Speaker 1: spent about ten years at university was trying to find 119 00:08:12,236 --> 00:08:15,516 Speaker 1: an experiment that would convince anybody else of that, and 120 00:08:15,556 --> 00:08:19,516 Speaker 1: he couldn't. So Timman has sort of there's ten years 121 00:08:19,516 --> 00:08:23,396 Speaker 1: in the wilderness, and he's not getting a lot of 122 00:08:23,476 --> 00:08:26,756 Speaker 1: encouragement from the scientific community in those ten years. Why 123 00:08:27,916 --> 00:08:33,796 Speaker 1: because the papers he's publishing are not convincing. So this 124 00:08:33,836 --> 00:08:38,036 Speaker 1: is is it sub tribute to his own innate suberness, 125 00:08:38,196 --> 00:08:42,156 Speaker 1: his own he convinced himself on some theoretical level that 126 00:08:42,636 --> 00:08:46,116 Speaker 1: there must be something there because he was driven by 127 00:08:46,236 --> 00:08:53,076 Speaker 1: that by his observation that the virus controlled the behavior 128 00:08:53,116 --> 00:08:57,716 Speaker 1: of the cells. Only genes control the behavior of cells, 129 00:08:58,396 --> 00:09:02,476 Speaker 1: and so the virus had to put it information in 130 00:09:02,516 --> 00:09:06,596 Speaker 1: the form of genes, and DNA was the form of genes. 131 00:09:07,556 --> 00:09:11,276 Speaker 1: He sort of religious he believed that therefore the information 132 00:09:11,436 --> 00:09:14,476 Speaker 1: RNA had to be read to DNA. And he wasn't 133 00:09:14,596 --> 00:09:18,036 Speaker 1: much of a chemist. He didn't think like a biochemist. 134 00:09:18,076 --> 00:09:22,356 Speaker 1: He thought like a geneticist. So the idea that RNA 135 00:09:22,476 --> 00:09:27,556 Speaker 1: could template DNA made sense to him as words, but 136 00:09:27,876 --> 00:09:31,876 Speaker 1: he had never actually done an experiment that looked at that. I, 137 00:09:32,076 --> 00:09:35,036 Speaker 1: on the other hand, had spent those ten years doing 138 00:09:35,676 --> 00:09:39,316 Speaker 1: that form of experiment with all sorts of different biological 139 00:09:39,396 --> 00:09:43,156 Speaker 1: materials and all sorts of different ways. That was my 140 00:09:43,236 --> 00:09:46,076 Speaker 1: bread and butter. Yeah. So yeah, let's let's talk about 141 00:09:46,076 --> 00:09:49,276 Speaker 1: your entry into this. So Don Keudy is up in 142 00:09:49,276 --> 00:09:53,716 Speaker 1: Wisconsin tilting in a windmill. Yes, and David Baltibor decides 143 00:09:53,756 --> 00:09:59,396 Speaker 1: to join in the windmill tilting. At what point do 144 00:09:59,476 --> 00:10:04,116 Speaker 1: you does this battle attract you? I mean, I know 145 00:10:04,356 --> 00:10:08,396 Speaker 1: exactly what form because I had been working on a 146 00:10:08,516 --> 00:10:12,996 Speaker 1: virus called vesiculostalmatitis virus, and we had discovered that it's 147 00:10:13,996 --> 00:10:20,556 Speaker 1: the complement of the sense strand of RNA. So it's 148 00:10:20,556 --> 00:10:23,916 Speaker 1: a senseless strand that acts solely as a template to 149 00:10:24,036 --> 00:10:29,516 Speaker 1: make sense strands. And if you think about that, a 150 00:10:29,596 --> 00:10:33,556 Speaker 1: virus like that can't just go into a cell and 151 00:10:33,716 --> 00:10:37,676 Speaker 1: take over the cell because it has to copy it's 152 00:10:37,796 --> 00:10:40,956 Speaker 1: RNA into messenger RNA. And the only way it can 153 00:10:40,996 --> 00:10:43,436 Speaker 1: do that is if either the cell has an enzyme 154 00:10:43,476 --> 00:10:45,876 Speaker 1: to do that, and we had looked for such a 155 00:10:46,316 --> 00:10:49,796 Speaker 1: enzyme could never find one, or if the enzyme was 156 00:10:49,836 --> 00:10:54,276 Speaker 1: in the virus particle. So I had looked for it 157 00:10:54,356 --> 00:10:58,716 Speaker 1: in the virus particle and found that the virus particle 158 00:10:58,796 --> 00:11:03,356 Speaker 1: had an RNA dependent RNA plumb race that copied the 159 00:11:04,316 --> 00:11:08,076 Speaker 1: senseless strand into a sense strand, and that's clearly how 160 00:11:08,156 --> 00:11:11,236 Speaker 1: infection got started. It and suddenly I opened up a 161 00:11:11,236 --> 00:11:14,996 Speaker 1: whole field of negative strand viruses. So now it became 162 00:11:15,236 --> 00:11:19,716 Speaker 1: trivial to say, well, you know, maybe Howard has something. 163 00:11:20,276 --> 00:11:23,676 Speaker 1: Let's have a look at the virus particles of RN 164 00:11:23,756 --> 00:11:28,156 Speaker 1: tumb virus. They might have an enzyme that copies are 165 00:11:28,236 --> 00:11:30,156 Speaker 1: an agency in it. Oh, I see. Once you had 166 00:11:30,196 --> 00:11:33,796 Speaker 1: made the insight that these viruses are carrying around their 167 00:11:33,836 --> 00:11:37,836 Speaker 1: own photocopiers or whatever it is, right, they have a 168 00:11:37,836 --> 00:11:40,716 Speaker 1: little a little in house xerox, you're like, oh, let's 169 00:11:40,756 --> 00:11:45,156 Speaker 1: just look for the maybe these are everywhere versions of them. 170 00:11:45,196 --> 00:11:48,036 Speaker 1: The minute you find the enzyme and the one you're 171 00:11:48,076 --> 00:11:50,476 Speaker 1: working on, is it instant that you think about what 172 00:11:50,516 --> 00:11:52,956 Speaker 1: Howard's doing or is it something you pops into your 173 00:11:52,996 --> 00:11:54,756 Speaker 1: head six months later. I'm just so curious about that 174 00:11:54,836 --> 00:11:59,836 Speaker 1: kind of what does that insight mean? I think it 175 00:11:59,876 --> 00:12:04,076 Speaker 1: wasn't very long. We did one other thing first, which 176 00:12:04,156 --> 00:12:07,076 Speaker 1: is we wanted to extend it to other viruses that 177 00:12:07,356 --> 00:12:10,836 Speaker 1: looked the same in the electron microscope, and we found 178 00:12:10,956 --> 00:12:15,076 Speaker 1: a number of other negative strands viruses right away. And 179 00:12:15,116 --> 00:12:18,196 Speaker 1: then I said, where else can we carry this idea to? 180 00:12:18,316 --> 00:12:21,556 Speaker 1: And I said, well, how about RNA tumor viruses? How 181 00:12:21,556 --> 00:12:24,716 Speaker 1: hard was it to find this particular enzyme? Is that? 182 00:12:25,036 --> 00:12:29,316 Speaker 1: Is it trivial? Oh? Really, it's really the two two 183 00:12:29,356 --> 00:12:33,996 Speaker 1: days of experiments two days. So it's just the idea 184 00:12:34,116 --> 00:12:36,916 Speaker 1: of knowing where to look and what to look for 185 00:12:37,076 --> 00:12:40,756 Speaker 1: and what to look for. Right, naive and weird question. 186 00:12:41,316 --> 00:12:45,396 Speaker 1: Do you know what you've done at the time? Yeah, 187 00:12:45,436 --> 00:12:48,956 Speaker 1: I knew what we had done in terms of cancer. 188 00:12:49,556 --> 00:12:52,636 Speaker 1: It was clear that we had broken over cancer research. 189 00:12:53,556 --> 00:12:58,796 Speaker 1: I didn't know what else we'd done. HIV hadn't been discovered. 190 00:12:58,796 --> 00:13:02,916 Speaker 1: I didn't know we had set up the understanding of HIV. 191 00:13:03,676 --> 00:13:08,436 Speaker 1: I didn't know that the genome of humans and all 192 00:13:08,556 --> 00:13:13,116 Speaker 1: organisms has lots of reverse transcribed DNA in It comes 193 00:13:13,116 --> 00:13:16,516 Speaker 1: from various sources. So it was much richer and more 194 00:13:16,516 --> 00:13:22,716 Speaker 1: complex than I could say with any assurance except for 195 00:13:22,796 --> 00:13:26,716 Speaker 1: the implications for cancer. Yeah, we're gonna talk a little 196 00:13:26,716 --> 00:13:29,876 Speaker 1: bit about HIV for a moment, undo a kind of 197 00:13:29,916 --> 00:13:35,996 Speaker 1: alternate history. If HIV arrives as a force ten years earlier, 198 00:13:36,156 --> 00:13:41,876 Speaker 1: in sixty seven, not seventy seven, what happens scientifically medically disaster. 199 00:13:42,756 --> 00:13:46,676 Speaker 1: The worst thing that can happen, and it was proved 200 00:13:46,756 --> 00:13:51,876 Speaker 1: in the HIV epidemic, is not to know what's causing 201 00:13:51,876 --> 00:13:57,996 Speaker 1: a disease, because that gives liberty to fantasy, and one 202 00:13:58,036 --> 00:14:01,396 Speaker 1: person's fantasy is as good as another's. So you don't 203 00:14:01,396 --> 00:14:05,036 Speaker 1: know who to believe. The public doesn't know what to believe. 204 00:14:06,236 --> 00:14:08,436 Speaker 1: You don't know how it's spread, You don't know if 205 00:14:08,436 --> 00:14:13,956 Speaker 1: it is in factious. The early days of the HIV epidemic, 206 00:14:14,196 --> 00:14:18,836 Speaker 1: there are all sorts of theories about homosexual sex poppers, 207 00:14:19,156 --> 00:14:22,596 Speaker 1: drugs people were taking. Until you knew it was a virus, 208 00:14:23,196 --> 00:14:25,756 Speaker 1: you didn't know how to intervene. You didn't know what 209 00:14:25,796 --> 00:14:30,356 Speaker 1: to do to protect yourself. So HIV is more than 210 00:14:31,196 --> 00:14:34,676 Speaker 1: a virus. It's a retrovirus, and it's operating by the 211 00:14:34,756 --> 00:14:38,916 Speaker 1: very principles that you intem and uncovered. But absent that knowledge, 212 00:14:39,036 --> 00:14:40,876 Speaker 1: we could know it was infectious and know it was 213 00:14:40,916 --> 00:14:43,676 Speaker 1: a virus, but not be able to We couldn't find it. 214 00:14:43,716 --> 00:14:46,596 Speaker 1: Couldn't find it. You can't find it unless you know 215 00:14:46,676 --> 00:14:50,236 Speaker 1: it's this particular class of right. It was the search 216 00:14:50,476 --> 00:14:56,956 Speaker 1: for reverse transcripts in the virus particles that opened up 217 00:14:56,956 --> 00:14:59,356 Speaker 1: the knowledge that it was a virus that was causing 218 00:14:59,356 --> 00:15:05,436 Speaker 1: the disease. Yeah. Yeah. And then secondarily, you can't even 219 00:15:05,516 --> 00:15:09,436 Speaker 1: begin to design drugs against it because aren't am I 220 00:15:09,516 --> 00:15:12,476 Speaker 1: right that the first wave of successful drugs are all 221 00:15:12,556 --> 00:15:16,396 Speaker 1: those that at reversian ships. Yeah, yes, yeah, they are 222 00:15:16,396 --> 00:15:21,676 Speaker 1: attacking this very vulnerability. They are nucleodide analogs, so they 223 00:15:21,876 --> 00:15:26,196 Speaker 1: look like pieces of RNA. Describe in the most DNA 224 00:15:26,356 --> 00:15:29,716 Speaker 1: I mean, yes, describe the mechanism of that first wave 225 00:15:29,756 --> 00:15:34,756 Speaker 1: of successful anti HIV drugs. The way that you copy 226 00:15:35,276 --> 00:15:40,516 Speaker 1: RNA into DNA is by copying one nucleotide at a 227 00:15:40,636 --> 00:15:45,716 Speaker 1: time into its compliment by the complimentary rules that had 228 00:15:45,796 --> 00:15:48,676 Speaker 1: been laid down by Watson and Crick that A pairs 229 00:15:48,716 --> 00:15:53,476 Speaker 1: would t and g pears would see. What these drugs 230 00:15:53,516 --> 00:15:59,636 Speaker 1: were were analogs of the ATGC that fit into the 231 00:15:59,716 --> 00:16:04,796 Speaker 1: slot where the copying went on, but then couldn't be 232 00:16:04,836 --> 00:16:09,756 Speaker 1: extended further, so they terminated the growth of the DNAH 233 00:16:10,956 --> 00:16:13,716 Speaker 1: and they are that's what they're called chain terminators. And 234 00:16:13,836 --> 00:16:19,116 Speaker 1: the theoretical basis for that entire operation is the understanding 235 00:16:19,116 --> 00:16:22,476 Speaker 1: that this is a virus that is operating through the 236 00:16:22,516 --> 00:16:26,076 Speaker 1: principles of a verse right. If you didn't know that, 237 00:16:26,516 --> 00:16:29,356 Speaker 1: if you didn't ask that question, you wouldn't have found 238 00:16:29,356 --> 00:16:31,676 Speaker 1: the virus and we would have been in the wilderness. 239 00:16:32,516 --> 00:16:36,876 Speaker 1: So if it had come about ten years earlier before 240 00:16:37,036 --> 00:16:40,796 Speaker 1: we had the reverse transcript tase, it would have been 241 00:16:40,836 --> 00:16:43,436 Speaker 1: a lot longer before we understood that it was a virus. 242 00:16:44,036 --> 00:16:46,636 Speaker 1: If I don't know how long it would have been. 243 00:16:47,036 --> 00:16:50,236 Speaker 1: I'm wondering whether once the sort of dust settles on 244 00:16:50,276 --> 00:16:53,316 Speaker 1: the discovery of verse transcript tase, is there a moment 245 00:16:53,316 --> 00:16:56,676 Speaker 1: when your mind wanders and you start to think about 246 00:16:56,716 --> 00:16:59,196 Speaker 1: all of the lung Like I know you said immediately 247 00:16:59,236 --> 00:17:00,596 Speaker 1: it was clear it was going to have an impact 248 00:17:00,636 --> 00:17:03,756 Speaker 1: on cancer, But did it ever for example, did it 249 00:17:03,756 --> 00:17:06,516 Speaker 1: ever out of the blue occurred to you that wow, 250 00:17:07,076 --> 00:17:11,076 Speaker 1: what if we did have a consequential virus that came 251 00:17:11,076 --> 00:17:14,436 Speaker 1: along that operated, that was a retrovirus. Now we're in 252 00:17:14,476 --> 00:17:16,036 Speaker 1: a much stronger I mean, I wanted to do you 253 00:17:16,076 --> 00:17:18,316 Speaker 1: ever gain out any of these scenarios in your mind? 254 00:17:19,116 --> 00:17:23,636 Speaker 1: Not a whole lot, because because we had enough to 255 00:17:23,636 --> 00:17:27,396 Speaker 1: think about it now, I then became passionately interesting in 256 00:17:27,596 --> 00:17:32,476 Speaker 1: how you copy on RNA into a DNA. And when 257 00:17:32,516 --> 00:17:36,196 Speaker 1: I say, how there are all sorts of details of 258 00:17:36,276 --> 00:17:40,956 Speaker 1: that process that are just fascinating molecular biology. And so 259 00:17:41,596 --> 00:17:45,316 Speaker 1: there was an area in my lab which focused on that. 260 00:17:46,436 --> 00:17:51,196 Speaker 1: The other thing we focused on was retroviruses and their 261 00:17:51,236 --> 00:17:55,476 Speaker 1: ability to cause cancer because we had opened up a 262 00:17:55,636 --> 00:17:58,756 Speaker 1: field and I wanted to be part of that field, 263 00:17:59,516 --> 00:18:03,516 Speaker 1: and so I went out on a hunt for a 264 00:18:03,596 --> 00:18:07,836 Speaker 1: mouse virus that was as good as routs circumavirus as 265 00:18:07,916 --> 00:18:10,716 Speaker 1: an object of study, but you could do it in 266 00:18:10,756 --> 00:18:14,156 Speaker 1: the context of mass genetics, and so you really could 267 00:18:14,676 --> 00:18:20,716 Speaker 1: take advantage of the whole history of mass biology. And 268 00:18:20,876 --> 00:18:25,116 Speaker 1: I found one and which was it's called Abelson mirroring 269 00:18:25,196 --> 00:18:30,036 Speaker 1: leukemia virus, and it was the secret to understanding chronic 270 00:18:30,076 --> 00:18:33,356 Speaker 1: myologist leukemia in the end, I mean, because it turned 271 00:18:33,356 --> 00:18:37,116 Speaker 1: out to be a virus that used an enzyme that 272 00:18:37,756 --> 00:18:40,876 Speaker 1: was part of the very serious human disease. But I 273 00:18:40,876 --> 00:18:42,596 Speaker 1: didn't know that at the time. I mean, it was 274 00:18:42,676 --> 00:18:45,596 Speaker 1: just a model that fit what I wanted to do 275 00:18:45,636 --> 00:18:49,716 Speaker 1: in a lab, So I didn't think a whole lot 276 00:18:49,756 --> 00:18:53,956 Speaker 1: about where else there might be viruses like this, and 277 00:18:54,276 --> 00:18:57,316 Speaker 1: there were so many other people doing that right away. 278 00:18:57,756 --> 00:19:00,636 Speaker 1: Coming back to HIV for a moment, when it comes 279 00:19:00,676 --> 00:19:04,556 Speaker 1: time to construct these anti virals for HIV. You're obviously 280 00:19:04,556 --> 00:19:09,556 Speaker 1: borrowing the central scientific insight. Here are they also bill 281 00:19:09,636 --> 00:19:13,196 Speaker 1: borrowing from all of this subsequent filling in all the 282 00:19:13,196 --> 00:19:15,676 Speaker 1: gaps work. I mean, if you were saying you then 283 00:19:15,756 --> 00:19:19,676 Speaker 1: got really interested in how this process of yeah, they 284 00:19:19,756 --> 00:19:22,476 Speaker 1: are they taking at work and using that to help 285 00:19:22,516 --> 00:19:29,796 Speaker 1: construct construct drugs. Yes, yeah, yeah, yeah. For instance, the integrace. 286 00:19:30,276 --> 00:19:34,276 Speaker 1: I mean, we didn't discover integrace, but working out the 287 00:19:34,316 --> 00:19:38,636 Speaker 1: details of reverse transcription, ultimately you come to something which 288 00:19:38,636 --> 00:19:41,836 Speaker 1: has to go into the nucleus and associate itself with 289 00:19:41,916 --> 00:19:44,876 Speaker 1: a DNA and the nucleus, and that was an integrace. 290 00:19:45,236 --> 00:19:48,996 Speaker 1: So integrace inhibitors turn out to be the very best drugs, 291 00:19:49,956 --> 00:19:53,196 Speaker 1: and there were a number of others. Protease is a 292 00:19:53,236 --> 00:19:57,796 Speaker 1: proteas that's very important, cutting up proteins into white sized pieces, 293 00:19:59,076 --> 00:20:02,036 Speaker 1: and if you inhibit that, you can prevent the virus 294 00:20:02,036 --> 00:20:05,316 Speaker 1: from growing. And so there are protease inhibitors. So yeah, 295 00:20:05,316 --> 00:20:09,316 Speaker 1: every aspect of the virus that we've ever studied then 296 00:20:09,476 --> 00:20:13,676 Speaker 1: lends itself to the development of drug At the time 297 00:20:13,716 --> 00:20:17,036 Speaker 1: you're doing all this work, how large is your lab? Oh, 298 00:20:17,196 --> 00:20:22,236 Speaker 1: it's about five or six people, it's you, a couple 299 00:20:22,236 --> 00:20:27,916 Speaker 1: of students, a couple of post docs. It's tiny, small. 300 00:20:28,236 --> 00:20:31,356 Speaker 1: I mean I had only just moved to MT in 301 00:20:31,436 --> 00:20:36,196 Speaker 1: sixty eight. Yeah, so I didn't yet have a sort 302 00:20:36,196 --> 00:20:38,756 Speaker 1: of pipeline of people to me into the lab. What 303 00:20:38,916 --> 00:20:40,956 Speaker 1: grants so you have do you have at that moment? 304 00:20:41,516 --> 00:20:46,356 Speaker 1: I have grants from NIH, largely to do work on 305 00:20:47,196 --> 00:20:52,516 Speaker 1: mangovirus and poliovirus. I don't think I got any grants. 306 00:20:52,996 --> 00:20:55,196 Speaker 1: I certainly didn't get a grant to work on Darna 307 00:20:55,236 --> 00:20:59,196 Speaker 1: toumber viruses. And we did the negative strand virus work 308 00:20:59,236 --> 00:21:02,636 Speaker 1: without grants. We just use the money we had from 309 00:21:02,756 --> 00:21:07,076 Speaker 1: other sources. But how large are those grants this is 310 00:21:07,116 --> 00:21:12,036 Speaker 1: late sixties. Oh, they're probably one hundred thousand dollars. Was 311 00:21:12,076 --> 00:21:15,636 Speaker 1: a lot of money in those days. I don't remember, 312 00:21:16,596 --> 00:21:18,996 Speaker 1: do you when you said when you made that an observation, 313 00:21:19,036 --> 00:21:22,676 Speaker 1: and you're like, oh, maybe that is explains what tem 314 00:21:22,676 --> 00:21:25,556 Speaker 1: And has been puzzling over. I love the way in 315 00:21:25,596 --> 00:21:29,636 Speaker 1: which so the two of you contribute beautifully to this, 316 00:21:29,836 --> 00:21:33,236 Speaker 1: to the success of this problem, coming from different directions. 317 00:21:33,596 --> 00:21:37,676 Speaker 1: If tim And hasn't been puzzling over it, was that 318 00:21:37,756 --> 00:21:39,276 Speaker 1: thought still a bit in the back of your mind. 319 00:21:41,076 --> 00:21:46,236 Speaker 1: Perhaps not if nobody had been thinking about it, would 320 00:21:46,316 --> 00:21:50,396 Speaker 1: I have come to it. I don't know. It's a 321 00:21:51,116 --> 00:21:55,436 Speaker 1: very hard hypothetical too. Yeah, partly because I, as I said, 322 00:21:55,476 --> 00:21:58,756 Speaker 1: I knew knew about Howard's interest in work for that 323 00:21:58,796 --> 00:22:02,716 Speaker 1: whole ten year period. Yeah, I asked what was going 324 00:22:02,756 --> 00:22:05,956 Speaker 1: on in virology? That was one thing going on virology. 325 00:22:06,476 --> 00:22:11,596 Speaker 1: I'm curious about what has that experience taught you about 326 00:22:11,716 --> 00:22:16,396 Speaker 1: the way science ought to be structured. Well, one of 327 00:22:16,396 --> 00:22:22,716 Speaker 1: the most important things to me is that young people 328 00:22:23,636 --> 00:22:27,916 Speaker 1: often do things that are sort of off the beaten 329 00:22:27,916 --> 00:22:34,516 Speaker 1: track and can produce real change in the way we think. 330 00:22:35,436 --> 00:22:40,636 Speaker 1: And so it's very important to give young people that opportunity, 331 00:22:40,716 --> 00:22:45,396 Speaker 1: and that the way we've structured the educational process in science, 332 00:22:46,236 --> 00:22:51,276 Speaker 1: we don't give people enough independence early enough in their 333 00:22:51,316 --> 00:22:55,276 Speaker 1: careers to take full advantage of the time when I 334 00:22:55,316 --> 00:22:59,796 Speaker 1: think you sort of naturally have the most creative opportunities. 335 00:23:00,756 --> 00:23:03,876 Speaker 1: And so the fact that I was and I'm partly 336 00:23:03,956 --> 00:23:09,556 Speaker 1: modeling that statement on my own life because I managed 337 00:23:09,596 --> 00:23:13,236 Speaker 1: to get that kind of independence from very early on, 338 00:23:14,276 --> 00:23:16,076 Speaker 1: partly because of the people I chose to work with, 339 00:23:16,876 --> 00:23:21,116 Speaker 1: partly because I was I guess fairly aggressive about it, 340 00:23:22,436 --> 00:23:26,236 Speaker 1: and so I was making my own decisions in science 341 00:23:26,436 --> 00:23:31,956 Speaker 1: from the time I really started out. Most people don't 342 00:23:31,996 --> 00:23:36,876 Speaker 1: get that opportunity, and most people probably can't handle it, 343 00:23:37,436 --> 00:23:39,396 Speaker 1: but there are more people who can handle it than 344 00:23:39,796 --> 00:23:43,676 Speaker 1: are given the opportunity. So I have, as I've gone 345 00:23:43,676 --> 00:23:49,076 Speaker 1: on and built institutions, tried to build into that the 346 00:23:49,156 --> 00:23:53,236 Speaker 1: opportunity for young people to get that kind of freedom 347 00:23:53,276 --> 00:23:57,396 Speaker 1: as early as possible, so that they can take advantage 348 00:23:57,396 --> 00:24:00,356 Speaker 1: of the time when I think they're most creative and 349 00:24:00,676 --> 00:24:07,436 Speaker 1: they're also least burdened by personal responsibility. And today, when 350 00:24:07,476 --> 00:24:12,036 Speaker 1: people get out of their training thirty five if they're lucky, 351 00:24:12,076 --> 00:24:14,116 Speaker 1: by which time they have families, and they have also 352 00:24:14,196 --> 00:24:18,116 Speaker 1: two other responsibilities. And I think that that's a shame. 353 00:24:18,916 --> 00:24:21,716 Speaker 1: Does a young David Baltimore in twenty nineteen have a 354 00:24:21,716 --> 00:24:24,276 Speaker 1: harder or easier time of it than a David Baltimore 355 00:24:24,276 --> 00:24:29,676 Speaker 1: in nineteen fifty. I think it's harder now, but it's 356 00:24:29,676 --> 00:24:32,636 Speaker 1: not impossible. One thing I set up that a lot 357 00:24:32,636 --> 00:24:38,436 Speaker 1: of places have emulated is a fellows program at the 358 00:24:38,436 --> 00:24:42,116 Speaker 1: White Hidden Institute, which I started, which isn't a time 359 00:24:42,156 --> 00:24:45,996 Speaker 1: that people can be independent and yet not have done 360 00:24:45,996 --> 00:24:50,156 Speaker 1: a post door and only the very best people are 361 00:24:50,196 --> 00:24:53,596 Speaker 1: accepted in it, and it's just turned out one after 362 00:24:53,636 --> 00:24:57,596 Speaker 1: another great people. Thank you very much. There's something I 363 00:24:57,636 --> 00:25:00,356 Speaker 1: should tell you, because I don't think you know it. 364 00:25:00,916 --> 00:25:05,516 Speaker 1: And that's actually what happened. The day after I made 365 00:25:05,516 --> 00:25:11,316 Speaker 1: the discovery, Oh Nixon invaded Cambodi. You and m I 366 00:25:11,636 --> 00:25:15,956 Speaker 1: went on strike and I was in the streets supporting 367 00:25:15,996 --> 00:25:20,756 Speaker 1: my graduate getting out of jail, leading groups marching down 368 00:25:20,756 --> 00:25:25,636 Speaker 1: the streets of Gambridge for about five days, and then 369 00:25:25,676 --> 00:25:27,916 Speaker 1: I came back to the lab, thought it all out 370 00:25:27,956 --> 00:25:41,436 Speaker 1: and finished the experiments. Strange world we live in. This episode, 371 00:25:41,476 --> 00:25:45,756 Speaker 1: to me, really highlights how a scientists curiosity, conviction, and 372 00:25:45,996 --> 00:25:49,756 Speaker 1: creativity can all combine to one day help somebody face 373 00:25:50,196 --> 00:25:53,636 Speaker 1: perhaps the most devastating diagnosis they'll ever have to face. 374 00:25:54,396 --> 00:25:56,836 Speaker 1: And also it made me think about how giving young 375 00:25:56,916 --> 00:25:59,796 Speaker 1: sciences a chance to make their own choices and to 376 00:25:59,956 --> 00:26:02,596 Speaker 1: be creative, even when they're early on in their careers, 377 00:26:02,996 --> 00:26:07,316 Speaker 1: when expertise and experience seems to be extremely important, that's 378 00:26:07,356 --> 00:26:11,156 Speaker 1: good too. And as of course, as David Baltimore pointed out, 379 00:26:11,156 --> 00:26:13,956 Speaker 1: it takes more than one person's work to come up 380 00:26:13,996 --> 00:26:18,156 Speaker 1: with actual treatments that end up saving lives. The intellectual 381 00:26:18,236 --> 00:26:22,196 Speaker 1: generosity he's shown throughout his career and now into his 382 00:26:22,276 --> 00:26:25,356 Speaker 1: teaching life is exciting to think about, and it gives 383 00:26:25,396 --> 00:26:28,756 Speaker 1: me hope that many more problems we once saw as 384 00:26:28,756 --> 00:26:32,676 Speaker 1: the end of the road are in fact solvable now. 385 00:26:32,716 --> 00:26:36,116 Speaker 1: If you're interested. Malcolm Gladwell has actually dedicated an episode 386 00:26:36,156 --> 00:26:39,836 Speaker 1: of his podcast Revisionist History to the story of the 387 00:26:39,956 --> 00:26:44,356 Speaker 1: search for retroviruses, and it features David Baltimore. It's called 388 00:26:44,436 --> 00:26:47,356 Speaker 1: The Obscure Virus Club. I hope you'll go and listen. 389 00:26:49,676 --> 00:26:54,436 Speaker 1: Solvable is a collaboration between Pushkin Industries and the Rockefeller Foundation, 390 00:26:54,556 --> 00:26:58,596 Speaker 1: with production by Laura Hyde, Hester Kant, Laura Sheeter, and 391 00:26:58,676 --> 00:27:02,556 Speaker 1: Ruth Barnes from Chalk and Blade. Pushkin's executive producer is 392 00:27:02,636 --> 00:27:07,596 Speaker 1: Neil LaBelle. Research by Sheer, Vincent, engineering by Jason Gambrel 393 00:27:07,676 --> 00:27:12,116 Speaker 1: and the great folks at SI Studios. Original music composed 394 00:27:12,116 --> 00:27:16,276 Speaker 1: by Pascal Wise and special thanks to Maggie Taylor, Heather Fine, 395 00:27:16,476 --> 00:27:21,276 Speaker 1: Julia Barton, Carli Mgliori, Jacob Weisberg, and Malcolm Gladwell. You 396 00:27:21,316 --> 00:27:25,396 Speaker 1: can learn more about solving today's biggest problems at Rockefeller 397 00:27:25,476 --> 00:27:30,196 Speaker 1: Foundation dot org slash solvable. I'm Mave Higgins. Now go 398 00:27:30,476 --> 00:27:30,876 Speaker 1: solve it.