This is a machine transcription and therefore it may contain inaccuracies, errors, or mispronunciations. Notice an error you think needs changing? Please contact the Bitesize Bio team using this form: https://bit.ly/bsbtranscriptions 0 00:00:01.580 --> 00:00:03.550 Welcome to CRISPR Unedited, 1 00:00:03.870 --> 00:00:07.470 a bite-sized bio podcast hosted by an Anthony Adamson. 2 00:00:07.940 --> 00:00:10.830 Stay on CRISPR unedited. We chat to Matthew Cobb, 3 00:00:10.940 --> 00:00:14.310 professor Zoology at the University of Manchester and Popular Science writer. 4 00:00:14.490 --> 00:00:17.870 We kick off at the very start of the genetic age, back in the 1970s, 5 00:00:18.330 --> 00:00:22.430 The real beginning of genetic engineering, which was in, 6 00:00:22.530 --> 00:00:23.870 in 1972. 7 00:00:24.370 --> 00:00:28.870 And that's when the first series of papers were published, uh, 8 00:00:28.870 --> 00:00:30.070 in the autumn of that year, 9 00:00:30.360 --> 00:00:35.150 which enabled us for the very first time to very PRIs relatively precisely, 10 00:00:35.530 --> 00:00:40.030 uh, introduced, uh, genetic material from one organism to one species. 11 00:00:40.060 --> 00:00:43.750 From we move on to discuss the hot topic of scientific self-regulation and 12 00:00:44.030 --> 00:00:44.863 safeguard development. 13 00:00:45.440 --> 00:00:49.550 There was a, a really pioneering conference, wasn't there? Back in, was it 1975? 14 00:00:49.860 --> 00:00:54.070 Yeah, early 1975. So what you gotta remember is that the, uh, 15 00:00:54.620 --> 00:00:58.030 this idea of mixing up, uh, 16 00:00:58.510 --> 00:01:02.030 d n a from different organisms, from bacteria, 17 00:01:02.620 --> 00:01:05.910 from viruses, different kinds of viruses, uh, 18 00:01:06.450 --> 00:01:08.270 had caused great con great concern. 19 00:01:08.530 --> 00:01:09.130 And finally, 20 00:01:09.130 --> 00:01:12.190 we end by discussing the promise of gene editing and what the future may hold. 21 00:01:12.290 --> 00:01:12.510 And 22 00:01:12.510 --> 00:01:16.790 Genetic engineering and gene editing may well be able to solve them in the ways 23 00:01:16.790 --> 00:01:21.230 you've suggested. Um, they're equally now, uh, tomatoes on the market, 24 00:01:21.230 --> 00:01:26.230 which are gonna supply, uh, particular vitamins or particular drugs. And that, 25 00:01:26.440 --> 00:01:30.790 again, may be a way of getting people to accept that, you know, this has, 26 00:01:31.210 --> 00:01:32.043 has been done 27 00:01:32.370 --> 00:01:34.950 All this and more in this episode of CRISPR Unedited. 28 00:01:43.810 --> 00:01:46.830 So, welcome to this podcast on the history of gene editing. 29 00:01:47.370 --> 00:01:49.150 I'm joined today by Matthew Cobb, 30 00:01:49.210 --> 00:01:52.910 who is a professor of Zoology at the University of Manchester. Matthew, uh, 31 00:01:52.910 --> 00:01:53.743 thank you for joining me. 32 00:01:54.480 --> 00:01:56.350 Thank you very much. Great to be here. 33 00:01:57.130 --> 00:02:00.390 Uh, so this is quite a timely podcast for a couple of reasons. First of all, 34 00:02:00.390 --> 00:02:03.030 Matthew, uh, you have a book out next month, I believe, on this, uh, 35 00:02:03.030 --> 00:02:04.030 that relates to this very topic. 36 00:02:04.060 --> 00:02:07.190 Yeah, yeah. It's, it's quite amazing. What a coincidence. Yeah. Um, 37 00:02:07.330 --> 00:02:11.830 so I've got a book out, uh, in the uk. It's called The Genetic Age, uh, 38 00:02:11.930 --> 00:02:16.470 our Perilous Quest to Edit Life. Uh, the book will be out in November, 39 00:02:16.890 --> 00:02:20.230 uh, in the us uh, confusingly under a different title, 40 00:02:20.390 --> 00:02:24.710 a rather more pompous one, which has nothing to do with me, called as God's, uh, 41 00:02:24.930 --> 00:02:29.350 um, a Moral History of the Genetic Age. But anyway, 42 00:02:29.420 --> 00:02:31.990 same book inside. It's got a different title and different color, but yes, 43 00:02:32.170 --> 00:02:34.230 that's, that, that's why I'm here, I suspect. 44 00:02:34.780 --> 00:02:38.270 Well, it sounds, sounds very dramatic in the, in the US at least. Um, and well, 45 00:02:38.270 --> 00:02:42.070 the second reason as well for this timeliness of this podcast is it's been 10 46 00:02:42.070 --> 00:02:46.670 years since the landmark CRISPR paper from down in chimpanzee in science, um, 47 00:02:46.760 --> 00:02:49.590 which of course led to that Nobel Prize a couple years ago into 20. 48 00:02:50.450 --> 00:02:53.950 And in those 10 years, we've seen the rise of that term, gene editing, 49 00:02:53.950 --> 00:02:57.270 which is just everywhere these days in the scientific literature. Um, 50 00:02:57.450 --> 00:02:59.520 but this term's been around a lot longer than that, hasn't it, Matthew? 51 00:03:00.470 --> 00:03:03.920 Well, yeah, I mean, it's not only the, the, the 10th anniversary of, uh, 52 00:03:04.800 --> 00:03:05.800 PON DA's paper. 53 00:03:06.070 --> 00:03:10.720 It's the 50th anniversary of the real beginning of 54 00:03:10.910 --> 00:03:13.880 genetic engineering, which was in, in 1972. 55 00:03:14.420 --> 00:03:19.120 And that's when the first series of papers were published, uh, 56 00:03:19.140 --> 00:03:20.360 in the autumn of that year, 57 00:03:20.650 --> 00:03:24.920 which enabled us for the very first time to very pres relatively 58 00:03:25.110 --> 00:03:29.600 precisely, uh, introduce, uh, genetic material from one organism, 59 00:03:29.600 --> 00:03:34.280 from one species, from one whole group, or, you know, from a virus into, uh, 60 00:03:34.280 --> 00:03:39.040 another organism. And that was the, the beginning of, well, 61 00:03:39.040 --> 00:03:42.480 what I've called the genetic age. Everything that's happened subsequently, 62 00:03:42.480 --> 00:03:46.760 including CRISPR and future methods of base editing and all the rest, 63 00:03:47.460 --> 00:03:50.320 no matter what the differences in the technology, which were enormous, 64 00:03:50.670 --> 00:03:53.640 they can all trace themselves back to that paper, 65 00:03:54.560 --> 00:03:57.960 although series of papers in the autumn of 1972. 66 00:03:58.460 --> 00:04:01.480 And what's interesting is that from the very beginning, 67 00:04:02.110 --> 00:04:06.320 because this is not simply scientific work, this has always had, uh, 68 00:04:06.520 --> 00:04:09.560 a practical application to it, or there's been, 69 00:04:09.560 --> 00:04:12.400 there's been hovering in the background from the very beginning. 70 00:04:12.490 --> 00:04:14.560 There have been concerns about safety, 71 00:04:14.650 --> 00:04:19.440 about how we're going to use this technology much as there have been 72 00:04:19.440 --> 00:04:22.240 over previous technologies that have been created, 73 00:04:22.240 --> 00:04:25.040 great anxieties from steam engines to, you know, 74 00:04:25.420 --> 00:04:28.200 the atomic power or, or whatever the, 75 00:04:28.380 --> 00:04:31.840 the genetic age is what we've been living in in the last 50 years. 76 00:04:31.860 --> 00:04:35.760 And it's shaped not only science, technology, medicine, 77 00:04:36.180 --> 00:04:41.160 but also culture. Uh, where would the world be without Jurassic Park? Uh, 78 00:04:41.260 --> 00:04:43.600 and that's, you know, so when you think of it in that way, 79 00:04:43.990 --> 00:04:46.400 it's not simply a matter of a series of discoveries we've made, 80 00:04:46.400 --> 00:04:51.080 but it's also about how those discoveries have course concern. 81 00:04:51.540 --> 00:04:55.960 And scientists in particular have been at the forefront of actually raising 82 00:04:55.960 --> 00:04:59.520 those issues. That, that's what I find particularly fascinating. Uh, 83 00:04:59.710 --> 00:05:02.520 just to conclude on this, a bit of a hurrah for geneticists. You know, 84 00:05:02.640 --> 00:05:05.280 'cause scientists have done all sorts of things, uh, in the past, 85 00:05:05.460 --> 00:05:10.280 but genetics is the only field in 86 00:05:10.280 --> 00:05:14.440 which scientists have taken a lead, said, 87 00:05:14.670 --> 00:05:17.120 this experiment is very worrying. 88 00:05:17.620 --> 00:05:22.520 We are not going to do it for a while until certain safety protocols 89 00:05:22.540 --> 00:05:26.920 can be, uh, implemented. And it's quite extraordinary that the physicists, 90 00:05:26.940 --> 00:05:29.080 for example, are working on the Manhattan Project. 91 00:05:30.190 --> 00:05:34.880 They were very concerned because when the project was finally coming to 92 00:05:34.980 --> 00:05:38.000 its, uh, its combination, the Germans had been defeated. 93 00:05:38.380 --> 00:05:43.040 And so the whole reason why they were racing to build the atomic bomb had 94 00:05:43.040 --> 00:05:46.520 disappeared. And yet it was still going to be used against Japan. 95 00:05:46.520 --> 00:05:50.800 And so many of the physicists were very unhappy about that for fairly obvious 96 00:05:50.850 --> 00:05:54.400 moral reasons. But they didn't actually stop work. They were open letter, 97 00:05:54.470 --> 00:05:56.640 they were letters. They complained, they argued, 98 00:05:56.640 --> 00:05:58.680 but they didn't actually stop work. And yet, 99 00:05:58.750 --> 00:06:03.480 four times in the history of genetic engineering, uh, 100 00:06:03.580 --> 00:06:08.080 in 1971, in 1974, in 2012, 101 00:06:08.140 --> 00:06:09.800 and most recently in 2019, 102 00:06:10.320 --> 00:06:15.120 researchers have either argued there should be a pause on research or have 103 00:06:15.320 --> 00:06:17.240 actually implemented it. So I think that in that, 104 00:06:17.240 --> 00:06:20.520 that's what interests not just simply amazing technology, which has, you know, 105 00:06:21.070 --> 00:06:25.040 transformed all sorts of parts of our lives affected culture, 106 00:06:25.260 --> 00:06:28.800 but it's also had this interaction with the, the social sphere. 107 00:06:29.930 --> 00:06:33.790 And I suppose in terms of that self-regulation, um, and geneticists, 108 00:06:34.770 --> 00:06:38.760 there was a, a really pioneering conference, wasn't there, back in, was it 1975? 109 00:06:39.070 --> 00:06:43.600 Yeah, early 1975. So what you've gotta remember is that the, uh, 110 00:06:44.150 --> 00:06:47.200 this idea of mixing up, uh, 111 00:06:47.680 --> 00:06:51.080 d n a from different organisms, from bacteria, 112 00:06:51.630 --> 00:06:55.120 from viruses, different kinds of viruses, uh, 113 00:06:55.700 --> 00:06:58.760 had caused great con great concern that the starting point was, 114 00:06:58.940 --> 00:07:02.960 was the work of Paul Berg, who won his Nobel Prize, uh, for this in 1980. 115 00:07:03.340 --> 00:07:07.120 And what Berg was really interested in was trying to understand how 116 00:07:08.430 --> 00:07:12.520 mammalian genes worked, which was virtually nothing was known about this. 117 00:07:12.520 --> 00:07:15.520 At the beginning of the 1970s. We had some idea about bacteria, 118 00:07:16.080 --> 00:07:19.920 bacterial genes in particular, things like the LAC on and so on. And so, 119 00:07:19.920 --> 00:07:23.440 what he thought was, okay, if I, we understand how the LAC on works, 120 00:07:23.500 --> 00:07:28.210 and we can put it, we could put, if we could put that into a mammalian cell, 121 00:07:28.480 --> 00:07:32.210 into a cell line, then we could get some idea of what the cell does, 122 00:07:32.210 --> 00:07:35.690 because it would have these instructions and we'd know what we'd expect it to do 123 00:07:36.350 --> 00:07:39.810 and what happens. So that was quite an interesting idea. 124 00:07:40.310 --> 00:07:44.530 And he was developing tools to do this lot along with a lot of other people in 125 00:07:44.730 --> 00:07:48.650 Stanford. And what he also decided to, 126 00:07:48.650 --> 00:07:52.090 he had a new PhD student called Janet Mertz, and he said, okay, well, 127 00:07:52.230 --> 00:07:56.490 if we're gonna use, um, uh, SV 40, which is a, 128 00:07:57.490 --> 00:08:02.370 a, uh, uh, a virus that causes, uh, tumors in, uh, 129 00:08:02.730 --> 00:08:05.050 hamster cells. So it's, it's something that people were very interested. 130 00:08:05.210 --> 00:08:09.170 'cause at the time, everybody, there's this very fashionable idea that, um, 131 00:08:10.380 --> 00:08:13.680 cancer was caused by viruses, all cancers, clearly some are. 132 00:08:13.700 --> 00:08:16.760 But it was the idea that, yeah, cancer is a viral disease. 133 00:08:17.020 --> 00:08:20.760 And so they was trying to study SV 40, and it infects, obviously, 134 00:08:20.760 --> 00:08:24.240 it infects mammalian cells. So they thought, okay, um, we can, 135 00:08:25.550 --> 00:08:28.320 what would happen if we put sv, he was, 136 00:08:28.420 --> 00:08:33.360 his primary interest was to use Ssv 40 to take the LAC gene and 137 00:08:33.360 --> 00:08:36.600 put it into, uh, a human cell or a mammalian cell. 138 00:08:37.100 --> 00:08:38.760 But he also thought for this PhD student, 139 00:08:38.760 --> 00:08:40.040 why don't we do the opposite experiment? 140 00:08:40.040 --> 00:08:43.400 Why don't we get the s just see what happens if we get the SV 40 potentially 141 00:08:43.470 --> 00:08:47.560 cancerous, uh, gene, uh, and put it into e coli, 142 00:08:47.850 --> 00:08:50.800 which is, as everybody knows, a, a gut bacterium. 143 00:08:51.380 --> 00:08:56.120 And when a man called Bob Pollack, uh, cold Spring Harbor heard of this in 1971, 144 00:08:56.580 --> 00:08:59.360 he said, what, you're gonna get a cancer causing gene, 145 00:08:59.360 --> 00:09:03.240 and you're gonna stick it into something that lives in our gut. You are crazy. 146 00:09:03.700 --> 00:09:06.480 And he basically said that to Bergen, told him to get lost, 147 00:09:06.540 --> 00:09:09.920 and eventually thought about it a lot, and then said, well, actually, yeah, 148 00:09:09.920 --> 00:09:13.080 it might be dangerous. And I don't really care about that experiment anyway. 149 00:09:13.390 --> 00:09:16.280 It's not really what I'm interested in, so, okay, I won't do it. 150 00:09:16.300 --> 00:09:18.520 So that was the first time, and it was all done in private. 151 00:09:18.520 --> 00:09:22.040 Nobody knew about this. But what happened is, 152 00:09:22.110 --> 00:09:25.560 with the development of Berg's method, uh, 153 00:09:25.860 --> 00:09:30.840 for using phage to the phage bacterium to get the whole 154 00:09:30.840 --> 00:09:34.360 of the e the, uh, LAC on from e coli, 155 00:09:34.420 --> 00:09:39.000 and then put that, uh, into a, uh, 156 00:09:39.390 --> 00:09:42.600 into a cell, um, very quickly, 157 00:09:43.070 --> 00:09:46.880 that quite cumbersome method, which he won his Nobel Prize for what I mean, 158 00:09:46.880 --> 00:09:51.450 without a matter of months, had been, uh, streamlined, 159 00:09:51.600 --> 00:09:56.570 made more simple. Janet Me's PhD student was one time PhD student. Now, 160 00:09:56.870 --> 00:10:01.580 uh, had turned the system from using six complicated enzymes to using two. 161 00:10:02.080 --> 00:10:03.820 So people at the time said, well, you know, 162 00:10:03.820 --> 00:10:06.420 any high school student could do this. I think it's a bit of an exaggeration, 163 00:10:06.720 --> 00:10:10.540 but what's striking is that the innovation really got, really took off. 164 00:10:10.800 --> 00:10:13.940 And within months of these papers being published 50 years ago, 165 00:10:14.110 --> 00:10:19.060 there was also the realization by Stan Cohen and Herb Boyer that they could 166 00:10:19.270 --> 00:10:22.580 manipulate plasmids, these weird bits of, uh, 167 00:10:22.940 --> 00:10:24.700 circular d n a that you get in bacteria, 168 00:10:25.080 --> 00:10:29.860 and then use those plasmids as a way of transferring between bacteria. 169 00:10:29.880 --> 00:10:33.420 And that led to the idea very rapidly that, okay, you could, 170 00:10:33.420 --> 00:10:37.020 you could divert anything with this technique. And when that was published, 171 00:10:37.490 --> 00:10:40.740 that is what caused the initial concerns. Uh, 172 00:10:40.740 --> 00:10:43.940 first in 1973 at a conference, when Bur Boyer, 173 00:10:43.940 --> 00:10:46.980 who was supposed to be not saying anything, 'cause work hadn't been published, 174 00:10:47.280 --> 00:10:49.580 he couldn't resist telling these young researchers, 175 00:10:49.580 --> 00:10:53.820 I've done this amazing thing with Stanko. Uh, and they all went, oh my God. 176 00:10:54.080 --> 00:10:58.820 You know, this is really rather alarming. And that led to the, 177 00:10:58.880 --> 00:11:02.260 uh, American Association, well, the American Academy of Sciences, 178 00:11:02.500 --> 00:11:05.180 national Academy of Sciences in the U S A, setting up a, 179 00:11:05.580 --> 00:11:07.460 a group to think about what should happen, 180 00:11:08.000 --> 00:11:11.500 how they could control this technology, what should be the rules around it. 181 00:11:11.920 --> 00:11:15.020 And Berg was the, uh, put in charge of this commission. 182 00:11:15.020 --> 00:11:19.260 And what they ended up with was this conference at Il Ilmar, 183 00:11:19.260 --> 00:11:21.940 which is on the California coast. And, uh, 184 00:11:22.620 --> 00:11:26.620 Berg chose that place because his department at Stanford regularly went up 185 00:11:26.620 --> 00:11:29.500 there. So it was, it was somewhere they knew you. It was, you know, it's a, 186 00:11:29.930 --> 00:11:31.660 it's conference center on the coast. Very nice. 187 00:11:31.660 --> 00:11:34.140 They had this meeting about 180 scientists, 188 00:11:34.140 --> 00:11:38.580 mainly from the us but from all over the world. Uh, um, 189 00:11:38.810 --> 00:11:42.060 it's particularly significant, as I'll explain later on. 190 00:11:42.060 --> 00:11:45.660 There were also some Russian researchers there, or Soviet researchers, 191 00:11:46.120 --> 00:11:50.490 and they thrashed out over about four days in fairly heated, 192 00:11:51.150 --> 00:11:55.560 uh, circumstances, a bit like a really fractious student meeting, you know, 193 00:11:55.700 --> 00:11:59.960 so it was a lot of argument and toing and froing. And some of the, 194 00:12:00.500 --> 00:12:04.960 they'd had this moratorium, they'd agreed in the middle of 1974, not the, 195 00:12:05.020 --> 00:12:08.440 nobody would work on re what's now known as recombinant, d n a, 196 00:12:08.440 --> 00:12:12.920 so d n a from more than one species. Uh, and everybody agreed, okay, 197 00:12:12.920 --> 00:12:17.880 we won't do this until we know how we can do it safely. And, uh, at the meeting, 198 00:12:17.970 --> 00:12:22.600 there were, the meeting was designed to re to remove the moratorium, 199 00:12:22.600 --> 00:12:27.080 to come to, you know, there was no question, should we do this? It was simply, 200 00:12:27.460 --> 00:12:32.240 how can we do this? So everybody, you know, as you rightly teed this up, 201 00:12:32.240 --> 00:12:35.560 people praise this as an example of scientists coming to a solution, 202 00:12:36.140 --> 00:12:40.340 but they didn't actually question what the technology might be used for. 203 00:12:40.960 --> 00:12:45.260 And in particular, the whole debates are focused on safety. So, um, 204 00:12:45.390 --> 00:12:49.760 David Baltimore, uh, later when they know very quickly, when they know the no, 205 00:12:49.760 --> 00:12:54.310 very quickly won the Nobel Prize, shortly afterwards, uh, he was the chair, 206 00:12:54.570 --> 00:12:55.510 and he said, right, 207 00:12:55.520 --> 00:12:59.030 we're not gonna be discussing potential commercial applications. 208 00:12:59.560 --> 00:13:02.190 We're not gonna be discussing environmental consequences. 209 00:13:02.280 --> 00:13:06.110 We're not gonna be discussing potential use in biological warfare. 210 00:13:06.330 --> 00:13:10.470 So all the kind of moral issues or political issues were taken off the agenda. 211 00:13:10.530 --> 00:13:12.710 And they simply said, all we know about is bio safety. 212 00:13:13.050 --> 00:13:17.470 How can we do this safely? So it's interesting that the, in fact, there were, 213 00:13:17.470 --> 00:13:21.640 there, there were very detailed discussions, but they're all about, you know, 214 00:13:22.160 --> 00:13:26.080 hoods and extraction and, you know, buyer safety and that, you know, 215 00:13:26.910 --> 00:13:30.040 what, what p p e you gonna wear. They weren't about, Hmm, 216 00:13:30.550 --> 00:13:33.760 this might do something bad. Uh, and I think that's, that, 217 00:13:33.760 --> 00:13:37.000 that part of the mythology of ilr, 'cause scientists love it. 'cause hey, 218 00:13:37.000 --> 00:13:39.200 we took control of this. We came up with these criteria. 219 00:13:39.580 --> 00:13:43.960 We then in the US gave them to the National Institutes of Health, which said, 220 00:13:44.260 --> 00:13:49.050 we won't fund anybody who doesn't use these procedures, which are basically, 221 00:13:49.050 --> 00:13:53.970 you know, four, four levels, as everybody still knows, still uses, uh, of, 222 00:13:54.070 --> 00:13:58.990 of biosafety. They never had the force of law. They were never put into, 223 00:13:58.990 --> 00:14:02.110 they didn't bizarrely apply to the private sector. 224 00:14:02.970 --> 00:14:07.830 So the private sector companies that very soon began in the 225 00:14:07.830 --> 00:14:12.710 wake of, uh, the Boyer and Cohen method, uh, in particular Genentech, 226 00:14:12.720 --> 00:14:15.590 which was created shortly afterwards, um, 227 00:14:16.900 --> 00:14:18.750 they were completely exempt from these rules. 228 00:14:18.750 --> 00:14:23.090 They generally followed them because that was the sensible thing to do. 229 00:14:23.110 --> 00:14:26.410 You don't want any bad press so that after a cinema, 230 00:14:26.790 --> 00:14:31.170 you get this set of rules which are gonna be applied. And there is now, 231 00:14:31.420 --> 00:14:35.650 after you've had the meeting, a huge public row about it. I mean, 232 00:14:35.650 --> 00:14:39.450 it becomes an immense thing all over the world where people say, oh my God, 233 00:14:39.450 --> 00:14:42.810 this is terrifying. It's gonna, you know, we're all gonna die. Um, 234 00:14:44.270 --> 00:14:46.730 wasn't helped by the fact that in the uk for example, 235 00:14:46.880 --> 00:14:51.680 we'd had two outbreaks of smallpox, uh, from one, 236 00:14:51.680 --> 00:14:54.240 from a a a, well, both from lab leaks, 237 00:14:54.240 --> 00:14:56.840 one in circumstances we don't still understand. And, you know, 238 00:14:56.840 --> 00:15:00.360 people had died from this. So there were, it wasn't just craziness, you know, 239 00:15:00.360 --> 00:15:03.440 it was just that weird seventies thing. People were, 240 00:15:04.020 --> 00:15:08.860 had legitimate reasons to be concerned about this, but amazingly, 241 00:15:08.890 --> 00:15:09.723 rapidly, 242 00:15:10.280 --> 00:15:13.610 rapidly when it became apparent that you could do the experiment safely, 243 00:15:13.760 --> 00:15:17.610 that there people weren't gonna die of cancer or whatever. 244 00:15:18.430 --> 00:15:19.930 And also, goodness me, 245 00:15:19.930 --> 00:15:24.850 there was potentially an awful lot of money to be made from this by 1980, 246 00:15:25.680 --> 00:15:30.680 this kind of four year crazy intense debates all over the world 247 00:15:30.680 --> 00:15:34.720 about what regulations we should have just kind of evaporated. Uh, 248 00:15:34.820 --> 00:15:37.560 it was also linked to political changes. You've gotta remember, you know, 249 00:15:37.560 --> 00:15:41.680 all this is linked up to society. It's not just scientists or biotech geniuses. 250 00:15:42.100 --> 00:15:44.520 Uh, this is when Thatcher comes to power in the uk. 251 00:15:44.520 --> 00:15:47.560 It's when Reagan comes to power in the US and deregulation, 252 00:15:47.560 --> 00:15:50.480 getting rid of all the, the, the red tape. Let's cut the red tape. 253 00:15:51.620 --> 00:15:54.440 And so this stuff, we don't need to worry about that. Let's just let it rip. 254 00:15:54.440 --> 00:15:57.640 You know, we gotta start making money. The whole global economies in the state. 255 00:15:57.970 --> 00:16:02.360 These people, for example, Genentech, come up with this way of making, uh, 256 00:16:02.870 --> 00:16:07.480 insulin, using, uh, using effectively the, 257 00:16:07.480 --> 00:16:10.960 the human gene. It's the first time this could be done. They use the, the human, 258 00:16:11.460 --> 00:16:14.840 uh, the sequence of human insulin. 'cause up until then, 259 00:16:14.840 --> 00:16:18.720 you had to use animal insulins insulin, which isn't exactly the same. Uh, 260 00:16:18.740 --> 00:16:20.160 you had to get it out of calves, 261 00:16:20.180 --> 00:16:21.480 How to combo by as well, I imagine. Yeah, 262 00:16:21.550 --> 00:16:25.120 Yeah. Well, you, well, there are a lot of calves die. So you get, you know, 263 00:16:25.260 --> 00:16:28.560 it was a byproduct of the meat industry, basically. You get the pancreas, 264 00:16:28.560 --> 00:16:31.480 lobb it out, send it off to the lab, but then kind of isolates it. 265 00:16:31.660 --> 00:16:35.840 But now you can make this stuff in vats. And it was better in a way than the, 266 00:16:35.900 --> 00:16:37.480 uh, the previous version. Not 267 00:16:37.480 --> 00:16:38.313 Necessarily cheaper though. 268 00:16:38.790 --> 00:16:41.680 Well, it was supposed to be, uh, but bizarre, you know, 269 00:16:41.680 --> 00:16:43.080 this is one of the things. I mean, 270 00:16:43.230 --> 00:16:47.040 it's because it's not simply a matter of scale, it's also, in particular, 271 00:16:47.060 --> 00:16:51.520 as we know, the us it's the, uh, the way that, uh, drugs are priced. 272 00:16:51.940 --> 00:16:53.600 And yeah. So we've seen this in particular, 273 00:16:53.700 --> 00:16:57.680 it should be the case because it's relatively straightforward to produce that 274 00:16:57.680 --> 00:17:00.920 this insulin should be, it's cheap as chips, but you know, 275 00:17:00.920 --> 00:17:05.560 in particular in the US is crazy, crazy prices. I mean, and this whole, you can, 276 00:17:05.560 --> 00:17:06.800 you can see, just to finish on this, 277 00:17:06.800 --> 00:17:11.600 this whole period closes with the two symbols. 278 00:17:11.600 --> 00:17:16.320 In 1980. On the same day, uh, Paul Berg wins his Nobel Prize, 279 00:17:17.270 --> 00:17:20.600 basically for inventing genetic engineering, 280 00:17:20.660 --> 00:17:24.800 or for making it turn it into a reality. And Genentech, uh, 281 00:17:24.980 --> 00:17:29.080 is put on the, uh, it goes public and goes onto Wall Street. 282 00:17:29.460 --> 00:17:33.680 And Herb Boyer, uh, becomes a multimillionaire Wow. Overnight, uh, 283 00:17:33.830 --> 00:17:38.240 because you know, everybody, this is just before Apple, uh, goes public. 284 00:17:38.240 --> 00:17:41.360 It's the first of the real excitement about biotech. Yeah, 285 00:17:41.360 --> 00:17:45.680 we can a lot of speculation. Uh, and, and immense, it was the biggest launch, 286 00:17:45.750 --> 00:17:48.600 most successful launch at the time that Wall Street had ever seen. 287 00:17:49.260 --> 00:17:50.080 So you've got the, 288 00:17:50.080 --> 00:17:55.080 the commercial wing and the academic wing kind of in, in fact, 289 00:17:55.080 --> 00:17:59.080 they were on the same page of the San Fro front page of the San Francisco, uh, 290 00:17:59.080 --> 00:18:02.520 Chronicle. Uh, you had Paul Berg winning his Nobel Prize, and, you know, 291 00:18:02.520 --> 00:18:05.640 Genentech takes Wall Street by storm, or whatever the headline was. 292 00:18:06.360 --> 00:18:08.480 I, I, I just think it's fascinating to hear the history of this, 293 00:18:08.480 --> 00:18:12.000 because there'll be so many people that list this podcast that might work in a 294 00:18:12.000 --> 00:18:15.040 lab. And for them, working with plasmids is just routine. You know, 295 00:18:15.040 --> 00:18:17.840 they're making them day in, day out, they're companies. 296 00:18:18.220 --> 00:18:21.800 And to hear the background where there was so much controversy from fear, 297 00:18:22.220 --> 00:18:23.053 you know, it, it, 298 00:18:23.430 --> 00:18:28.200 it's a really interesting way to view what we do on a day-to-day basis and how 299 00:18:28.200 --> 00:18:30.880 things progressed over time. Yeah. And you mentioned, you know, 300 00:18:30.900 --> 00:18:32.840 you know about these fears. Obviously the, 301 00:18:32.940 --> 00:18:35.920 the same kind of fears have always been around about gene editing as well, 302 00:18:35.920 --> 00:18:38.920 about CRISPR nine, about what are people gonna do with it? 303 00:18:39.430 --> 00:18:42.080 That concept of regulation I find really interesting, 304 00:18:42.080 --> 00:18:45.640 because an analogy I often use is, is, um, 305 00:18:46.260 --> 00:18:48.880 if I were to go and do an experiment that involved radioactivity, 306 00:18:49.680 --> 00:18:53.640 I can't order that radioactive material to my home address. I, I can't do that. 307 00:18:53.640 --> 00:18:56.680 Obviously, you need to work in an institution. It's got approvals in place, 308 00:18:56.680 --> 00:18:59.760 necessarily health and safety with Crispr Cas nine. 309 00:18:59.780 --> 00:19:03.240 I'm not totally certain that's the case right now. Maybe it should be, because, 310 00:19:03.820 --> 00:19:05.720 you know, these days companies have just, you know, 311 00:19:05.720 --> 00:19:07.640 jumped on the bandwagon as well with crispr. 312 00:19:07.640 --> 00:19:09.520 And there's so many commercial products out there. 313 00:19:09.830 --> 00:19:12.600 It's made my life much easier as a, as a scientist. 314 00:19:13.420 --> 00:19:15.920 But should we be regulating that supply that, you know, 315 00:19:15.920 --> 00:19:17.440 controlling who can buy these things? 316 00:19:17.870 --> 00:19:20.840 Well, there, there is a kind of regulation. So again, 317 00:19:20.840 --> 00:19:25.620 this is when it all interacts with, uh, with politics again. So I said that at, 318 00:19:25.680 --> 00:19:29.460 uh, at Ilmar, they didn't discuss, they wouldn't discuss, uh, genetic, 319 00:19:29.460 --> 00:19:32.460 they wouldn't discuss bio weapons. Although Baltimore said, 320 00:19:32.460 --> 00:19:36.140 this is potentially the most significant and terrifying application here, 321 00:19:36.140 --> 00:19:39.860 but we're not gonna talk about it. One of the reasons for that is that, um, uh, 322 00:19:40.110 --> 00:19:44.380 Nixon in 1969, president Nixon had just out of the blue said, okay, 323 00:19:44.380 --> 00:19:49.220 we're destroying all our stocks of traditional biological weapons. I mean, 324 00:19:49.220 --> 00:19:52.740 they didn't destroy all, they never do. Uh, but, you know, we're, we're, 325 00:19:52.740 --> 00:19:54.860 we're not gonna, we are not gonna develop anything new. 326 00:19:54.870 --> 00:19:59.260 We'll be fine just with anthrax or whatever they had developed, you know? Um, 327 00:19:59.480 --> 00:20:02.740 but that meant there was no active program of developing, uh, 328 00:20:03.320 --> 00:20:07.460 bio weapons in America. So I think the Americans could feel, well, actually, 329 00:20:07.460 --> 00:20:09.380 you know, maybe the politicians have sorted this out. 330 00:20:10.200 --> 00:20:14.620 It turns out that the five person Soviet delegation, 331 00:20:14.750 --> 00:20:16.740 which was composed of, uh, 332 00:20:16.740 --> 00:20:20.860 people who were kind of ridiculed by the young bucks of American molecular 333 00:20:21.020 --> 00:20:24.500 genetics, there were all these old guys in their sixties, uh, 334 00:20:24.560 --> 00:20:26.140 who just didn't know anything. 335 00:20:27.140 --> 00:20:31.210 Three of them had been involved in a decision taken two years earlier in the 336 00:20:31.210 --> 00:20:35.650 Soviet Union to develop, uh, an active bio weapons program. 337 00:20:36.190 --> 00:20:39.290 Wow. And they were actively developing. 338 00:20:39.290 --> 00:20:42.530 So they were there pretending to be these kind of nies who didn't understand 339 00:20:42.850 --> 00:20:46.530 anything, but in fact, they knew perfectly well how this could be used. And, 340 00:20:47.660 --> 00:20:50.440 uh, for complex reasons, uh, 341 00:20:51.260 --> 00:20:56.120 partly because this was a way of getting money for molecular genetics in the 342 00:20:56.120 --> 00:20:59.880 Soviet Union. They said to Brev, right, we will build you new bio weapons. 343 00:21:00.060 --> 00:21:02.760 We will fuse, you know, new microbes, uh, 344 00:21:02.760 --> 00:21:07.000 microbes and viruses together to make terrifying weapons. It took a long time, 345 00:21:07.780 --> 00:21:11.200 but by, uh, the middle of the eighties, they'd actually succeeded. 346 00:21:11.200 --> 00:21:14.200 And they were developing very worrying, new weapons. 347 00:21:14.420 --> 00:21:18.640 All this became apparent when there were a series of defectors in the 1980s. 348 00:21:19.180 --> 00:21:23.120 And, uh, eventually the collapse of the Soviet Union, uh, 349 00:21:23.860 --> 00:21:27.600 the West now knew exactly what had been going on. There were books published. 350 00:21:27.600 --> 00:21:30.720 I mean, I, you know, I, I just noticed that these guys were at the, 351 00:21:30.820 --> 00:21:33.200 who these guys were who were at Sima. Um, 352 00:21:33.340 --> 00:21:36.960 the actual groundwork of discovering all this has been done by either defectors 353 00:21:36.960 --> 00:21:39.840 or by, uh, academics interest in Soviet history. 354 00:21:41.020 --> 00:21:45.440 And that meant that when people now became very alarmed, because, uh, 355 00:21:45.440 --> 00:21:49.000 just as with nuclear weapons, after the collapse of the Soviet Union, 356 00:21:49.050 --> 00:21:51.880 there was all these bio weapons. 'cause there were, 357 00:21:51.880 --> 00:21:54.840 there were thousands and thousands of researchers all over the Soviet Union 358 00:21:54.970 --> 00:21:59.600 who'd been developing this either to kill people or to kill plants and animals. 359 00:21:59.600 --> 00:22:04.160 There were two kind of wings to this project. So you, the West then gets very, 360 00:22:04.160 --> 00:22:08.680 very alarmed about, uh, what if these, uh, 361 00:22:08.680 --> 00:22:13.440 techniques fall into the wrong hands? Right? And so it could be rogue states, 362 00:22:13.810 --> 00:22:17.360 terrorists. And then of course, with nine 11, 363 00:22:18.930 --> 00:22:21.670 the, at the beginning of the century, uh, 364 00:22:21.970 --> 00:22:25.470 the US in particular becomes absolutely terrified. There were, 365 00:22:25.530 --> 00:22:30.250 it wasn't only that 9 11, 9 11 younger listeners may not remember, well, no, 366 00:22:30.520 --> 00:22:34.770 nine 11 was followed virtually immediately by a series of, uh, 367 00:22:35.010 --> 00:22:39.370 envelopes containing anthrax that were sent around to various people in the, 368 00:22:39.470 --> 00:22:43.490 in the, in the u s a to the ca center, the, the ca capital in Washington. 369 00:22:43.510 --> 00:22:45.770 And so a number of people died by in ha you know, 370 00:22:45.770 --> 00:22:47.570 they opened the envelope and the spores come out. 371 00:22:48.190 --> 00:22:50.690 So there's a kind of real fear about bioterrorism. 372 00:22:50.690 --> 00:22:53.690 The letters were accompanied by Islamist rhetoric, 373 00:22:53.690 --> 00:22:57.890 but immediately the security services, I dunno how spotted that this, 374 00:22:58.160 --> 00:23:01.090 this was just kind, this, this wasn't real. It was somebody else. 375 00:23:01.590 --> 00:23:06.490 Almost certainly it was a, an, uh, an American scientist who committed sign, uh, 376 00:23:06.560 --> 00:23:08.090 suicide before he could be charged. 377 00:23:08.870 --> 00:23:13.490 But this meant that in the US you now have this growing concern about, 378 00:23:14.190 --> 00:23:16.810 uh, potential bio-terrorism. 379 00:23:16.810 --> 00:23:20.490 There was the development of the first gain of function studies. 380 00:23:21.070 --> 00:23:25.850 So people were starting to reconstruct or 381 00:23:25.850 --> 00:23:29.570 develop viruses because they thought it was interesting. I mean, 382 00:23:29.570 --> 00:23:32.250 it's first done completely by accident. They discovered that, uh, 383 00:23:32.520 --> 00:23:37.270 they were trying, some Australian researchers were trying to, uh, make, uh, 384 00:23:38.590 --> 00:23:42.470 mice susceptible. 'cause mice can be a terrible problem in Australia. 385 00:23:42.470 --> 00:23:44.430 There are a lot of marsupials, they're invasive species. 386 00:23:44.570 --> 00:23:47.320 And they were trying to find a bio weapon against the mice, 387 00:23:48.460 --> 00:23:50.320 and they were working on something called mouse px. 388 00:23:50.380 --> 00:23:54.840 And they discovered that they had inadvertently made a strain 389 00:23:55.180 --> 00:23:59.760 of, uh, mouse px that would not be affected by, 390 00:24:00.180 --> 00:24:03.320 uh, vaccines and mouse px, as the name kind of might indicate. 391 00:24:03.390 --> 00:24:05.200 It's very similar to smallpox. Mm-hmm. 392 00:24:05.300 --> 00:24:08.000 So these guys in Australia were absolutely terrified. 393 00:24:08.000 --> 00:24:12.160 They had inadvertently stumbled upon a way of making smallpox 394 00:24:13.630 --> 00:24:17.380 resistant to, uh, vaccines. So you, 395 00:24:17.680 --> 00:24:22.220 you start to get the development also of the various, uh, mini pandemics of the, 396 00:24:22.340 --> 00:24:24.820 the, you know, the spillover events, uh, 397 00:24:24.890 --> 00:24:29.020 that are occurring in China and in the Middle East, there's Mers, there's sars. 398 00:24:29.640 --> 00:24:34.460 And so the world is starting 15 years ago to start and get very antsy about 399 00:24:34.570 --> 00:24:37.780 this could all be weaponized. You get the development of synthetic biology, 400 00:24:38.800 --> 00:24:42.380 hacker culture, the idea that we can do this in our basement, and as you say, 401 00:24:42.380 --> 00:24:46.740 you can just order stuff, you know, so journalists would order over the, 402 00:24:46.850 --> 00:24:51.380 over the internet bits of the, the smallpox virus sequence, 403 00:24:51.600 --> 00:24:54.900 and they just get it in the post. You know, you send it to your home. 404 00:24:55.560 --> 00:25:00.180 So what the US government started to do in particular, and the UK, 405 00:25:00.180 --> 00:25:01.620 is to have, uh, 406 00:25:01.620 --> 00:25:06.540 systems whereby companies were supposed to be screening the sequences. You know, 407 00:25:06.540 --> 00:25:09.620 what exactly are you asking? You seen, you know, a little paperclip would pop, 408 00:25:09.620 --> 00:25:11.820 pop up and said, you seem to be ordering a bio weapon. 409 00:25:11.880 --> 00:25:16.260 Do you really want to do this? Or, you'd get men in black and, you know, 410 00:25:16.260 --> 00:25:18.460 black glasses charging into your door. 411 00:25:18.720 --> 00:25:21.460 But as the example of the journalist in London shows, 412 00:25:21.520 --> 00:25:24.980 you can actually order the bits and then assemble it. You know, 413 00:25:24.980 --> 00:25:27.820 if you're clever, not particularly clever. I mean, 414 00:25:28.760 --> 00:25:33.340 what's striking is that after the US invaded, uh, Afghanistan, 415 00:25:33.340 --> 00:25:36.060 after nine 11, they, uh, 416 00:25:36.250 --> 00:25:41.040 they found lots of documents written by the written by the 417 00:25:41.360 --> 00:25:44.120 Al-Qaeda leadership. And one of them said, yeah, 418 00:25:44.120 --> 00:25:47.800 the West keeps on saying that this bio weapon stuff is really easy. 419 00:25:48.500 --> 00:25:51.600 We should try it now. They didn't succeed. 420 00:25:51.660 --> 00:25:55.480 But actually it was all the rhetoric about, God, this is amazing. 421 00:25:55.600 --> 00:25:59.920 This is amazingly simple. People can use this to attack us. You know, 422 00:25:59.920 --> 00:26:03.840 we must control this. And the terrorists took notice, and they tried, 423 00:26:03.860 --> 00:26:07.320 but it turned out to be more complicated. So yeah, there is a, 424 00:26:07.320 --> 00:26:12.080 this real concern that has been going on in particular, it's been, you know, 425 00:26:12.740 --> 00:26:17.000 it was nine 11 that really kind of kickstarted it, the development of the, 426 00:26:17.700 --> 00:26:21.440 the recognition that there were potential new bio weapons that could be created 427 00:26:21.500 --> 00:26:23.440 by this relatively straightforward technology. 428 00:26:23.900 --> 00:26:28.560 And that then kind of feeds into the whole political and economic 429 00:26:29.030 --> 00:26:33.360 funding of research. And research is a guided into gain of function studies. 430 00:26:34.260 --> 00:26:38.400 And that in 2012 leads to them suddenly going, well, crikey, 431 00:26:38.400 --> 00:26:41.960 we've now made these viruses, you know, for example, bird flu. 432 00:26:42.660 --> 00:26:46.680 They'd made it, they deliberately made it transmissible through the air, 433 00:26:46.680 --> 00:26:50.320 which just seems, you know, by re respiration, why on earth would you do that? 434 00:26:50.340 --> 00:26:52.000 And the argument they have is, okay, 435 00:26:52.000 --> 00:26:56.950 well this will enable us to understand future pandemics. Well, you know, I, 436 00:26:57.020 --> 00:26:59.990 there's an argument about this, but my personal view is, well, you know, 437 00:26:59.990 --> 00:27:02.550 covid shows that it didn't actually help. 438 00:27:03.050 --> 00:27:04.070 No, absolutely not. 439 00:27:04.140 --> 00:27:08.430 Because of how molecular genetics has helped, has enabled us to beat it. 440 00:27:08.770 --> 00:27:13.110 It didn't enable us to predict what it was gonna do or in any way or form. 441 00:27:13.170 --> 00:27:15.150 But there is a big argument about this, I recognize. 442 00:27:15.450 --> 00:27:20.350 But the main thing is that just as in the seventies and eighties, 443 00:27:20.850 --> 00:27:24.950 people who weren't trained in basic micro microbiological techniques 444 00:27:25.420 --> 00:27:28.670 flooded into the area to start, you know, making new, uh, 445 00:27:28.670 --> 00:27:32.710 putting human genes into microbes and creating new drugs. 446 00:27:33.290 --> 00:27:35.590 The same thing happened 20 years ago, 447 00:27:36.010 --> 00:27:39.870 is that lots of people could get now get funding for doing research on these mi 448 00:27:40.110 --> 00:27:44.990 microbes, but didn't necessarily have the training to do so safely. 449 00:27:45.170 --> 00:27:48.950 And that has been continued, the continual argument thus far. 450 00:27:50.240 --> 00:27:55.020 Nothing bad has happened, but, you know, I think that's a matter of luck. 451 00:27:55.940 --> 00:27:58.940 I thought that continues. I wanna move away from, you know, some, sorry. Yeah. 452 00:27:59.240 --> 00:28:01.660 Als we've been talking about, obviously, um, 453 00:28:01.840 --> 00:28:04.100 and talk about some of the promises, because obviously Yeah, absolutely. 454 00:28:04.110 --> 00:28:09.060 We're in a, in a revolutionary era. Um, GNSS is not a new technology. And, 455 00:28:09.160 --> 00:28:09.620 you know, we, 456 00:28:09.620 --> 00:28:12.860 we can track the development GNS from recombinant d n A technology. 457 00:28:13.920 --> 00:28:14.900 In the early nineties. 458 00:28:15.080 --> 00:28:19.700 We saw Adjacents Land Max studies on Mega Nucleases first time 459 00:28:20.220 --> 00:28:23.860 demonstrating that if you generate a break in the D N A within a male yourself, 460 00:28:24.050 --> 00:28:27.020 then you can exploit the repair pathways that follow and make changes. 461 00:28:27.720 --> 00:28:31.580 And of course, then we had, um, uh, zinc fingers, tailings, 462 00:28:32.160 --> 00:28:36.380 and it was really CRISPR Cas nine that has democratized gene editing because 463 00:28:36.410 --> 00:28:40.740 it's so easy to use. Where do you see the future of gene editing? Um, 464 00:28:40.740 --> 00:28:44.420 because from speaking my perspective as a laboratory scientist, 465 00:28:44.530 --> 00:28:48.580 it's totally revolutionized how we approach research and the things we can do 466 00:28:48.580 --> 00:28:51.180 these days. But are we just still scratching the surface? 467 00:28:52.490 --> 00:28:56.390 Um, well, I think there's a, as a technique for discovery, 468 00:28:57.330 --> 00:29:01.870 uh, this is, I don't think you could imagine much better. It is, I mean, the, 469 00:29:01.890 --> 00:29:04.470 you know, obviously people are always fiddling around with it and making the, 470 00:29:04.650 --> 00:29:08.110 the, the, the guide RNAs more accurate and all the rest of it. 471 00:29:08.850 --> 00:29:12.830 But as a research tool, then this is, I mean, you know, 472 00:29:14.860 --> 00:29:18.870 your imagination literally is, is the limit. The problem is, 473 00:29:19.050 --> 00:29:21.470 the issue comes as, as always with these things is, well, 474 00:29:21.470 --> 00:29:23.710 how are you then gonna turn that into an application, 475 00:29:24.090 --> 00:29:28.390 either as a reliable therapy, a reliable, uh, 476 00:29:28.600 --> 00:29:32.070 technology that you could put into the fields, uh, 477 00:29:32.290 --> 00:29:37.070 or as some people wish to do as a reliable technology, 478 00:29:37.170 --> 00:29:38.710 you could then release into the wild, 479 00:29:39.250 --> 00:29:44.120 either in terms of altering populations or, uh, you know, 480 00:29:44.220 --> 00:29:48.720 de extincting, the, the, the big fantasy. Now, my, my own view is that the, 481 00:29:49.620 --> 00:29:53.200 the, the devil is always in the detail. And, you know, 482 00:29:53.200 --> 00:29:55.600 the science fiction of idea, okay, we can resurrect a, uh, 483 00:29:55.640 --> 00:29:58.310 a mammoth fairly quickly, 484 00:29:58.700 --> 00:30:02.990 kind of collapses under the weight of the actual immense technical genetic 485 00:30:03.510 --> 00:30:08.470 problems there are with doing that. On the other hand, curing diseases, 486 00:30:08.790 --> 00:30:13.390 I think there is, if it can be made safe, I mean, this is the problem. So, 487 00:30:13.570 --> 00:30:17.350 you know, genetic gene therapy has been around since before, 488 00:30:18.690 --> 00:30:21.470 um, Paul Berg's experiment. 489 00:30:22.090 --> 00:30:26.870 So the earliest attempts to try and use genes to cure genetic 490 00:30:26.950 --> 00:30:31.550 diseases were, were done in 1970, and then again in 1980. So these were, 491 00:30:31.700 --> 00:30:33.070 they didn't work. Uh, 492 00:30:33.330 --> 00:30:37.830 but these were attempts to try and solve genetic problems in, 493 00:30:37.850 --> 00:30:42.470 in humans. And there have been some remarkable successes, 494 00:30:42.490 --> 00:30:47.390 but the technology has been limited because, for example, uh, 495 00:30:47.420 --> 00:30:51.390 with the, you know, dealing with the bubble boy disease, SS E A S E I D, 496 00:30:51.390 --> 00:30:53.950 or skid, however you want to pronounce it, um, 497 00:30:55.450 --> 00:30:56.780 this could be resolved, 498 00:30:57.160 --> 00:31:01.860 but only by using vectors carrying the new 499 00:31:02.410 --> 00:31:04.900 gene that you couldn't control the insertion of. 500 00:31:05.560 --> 00:31:10.500 And this led to some patients being cured, other patients being cured, 501 00:31:10.520 --> 00:31:14.060 and then developing leukemia. Because the gene had gone, you know, the, the, 502 00:31:14.060 --> 00:31:19.020 the payload had been put in the wrong place and had inadvertently turned out 503 00:31:19.020 --> 00:31:22.780 that the, the vector actually wanted to hit a particular target. 504 00:31:22.880 --> 00:31:24.780 And that target in some, uh, 505 00:31:24.780 --> 00:31:28.740 people turn out to be this gene that if mutated would cause leukemia. 506 00:31:29.040 --> 00:31:29.873 So you've got this, 507 00:31:30.090 --> 00:31:32.980 It's that word control, though. I mean, the word use and control. 508 00:31:33.090 --> 00:31:36.660 Because when you think of the term gene editing, when you say editing something, 509 00:31:37.130 --> 00:31:39.860 it's like making a deliberate change. It's, you know, you, like, 510 00:31:39.880 --> 00:31:41.980 you precisely know what the outcome's gonna be. 511 00:31:41.980 --> 00:31:42.813 Well, that's, that's it, yeah. 512 00:31:42.960 --> 00:31:45.340 And how we have, we got the precision, I, 513 00:31:45.420 --> 00:31:48.020 I would argue probably not at this point in time. Like, like you say, 514 00:31:48.020 --> 00:31:51.060 it'll improve, but have we got that precision? 515 00:31:51.090 --> 00:31:54.380 Well, that's the No, clearly we haven't. I mean, we haven't enough. I mean, and, 516 00:31:54.400 --> 00:31:58.780 and this, this morning you've retweeted and i, I retweeted, uh, 517 00:31:59.050 --> 00:32:03.860 even the apparently safer base editing techniques, which look very exciting, 518 00:32:03.950 --> 00:32:07.420 could resolve, you know, single nucleotide diseases, uh, 519 00:32:07.530 --> 00:32:11.060 like sickle cell disease. I mean, you know, so there are, there are, 520 00:32:11.510 --> 00:32:15.420 there are tremendous potential applications here. And you just, 521 00:32:15.480 --> 00:32:18.780 you read the paper and you start, you go, crikey, that, that's amazing. 522 00:32:18.850 --> 00:32:22.380 This can work. You know, we could alter a single base bear, uh, 523 00:32:22.440 --> 00:32:26.580 and therefore cure somebody in without getting into any worries about, uh, 524 00:32:26.900 --> 00:32:30.980 germline editing, which would be done, uh, in, uh, in somatic cells. 525 00:32:30.980 --> 00:32:33.020 And you'd re-inject, you know, do them ex vivo, 526 00:32:33.020 --> 00:32:37.020 you'd then re-inject them and fantastic. You can now, you know, cure somebody. 527 00:32:37.040 --> 00:32:41.420 And there are individuals who have gone undergone experimental 528 00:32:42.340 --> 00:32:44.980 procedures. I think that's always the emphasis. This is experimental. 529 00:32:44.980 --> 00:32:47.060 People have incredibly bravely, 530 00:32:47.250 --> 00:32:51.140 they are literally being a Guinea pig and allowing them set their bodies to be 531 00:32:51.140 --> 00:32:56.140 used to understand. But the problem is, you know, the off target effects that, 532 00:32:56.560 --> 00:32:59.660 uh, I mean, I explained this to students that depending on, you know, 533 00:32:59.660 --> 00:33:02.940 the ordinary crispr, depending on when it, the state of the cell cycle, 534 00:33:03.690 --> 00:33:08.240 when you do it, it can have completely catastrophic effects. 535 00:33:08.240 --> 00:33:11.720 Sometimes you, you can lose whole chromosomes. I recently got that. 536 00:33:11.720 --> 00:33:14.600 So I talked to the students about this after our first and second year students. 537 00:33:14.980 --> 00:33:19.920 And one student wrote in his response or her responses, I don't understand, 538 00:33:20.470 --> 00:33:23.960 Cobb went on about off-target effects, but my lecturers never talk about that. 539 00:33:24.020 --> 00:33:27.720 It just seems to be really simple, which is true. And of course, 540 00:33:27.720 --> 00:33:32.120 both are true from an experimental, from a scientific point of view. I mean, 541 00:33:32.150 --> 00:33:32.990 to be brutal, you know, 542 00:33:32.990 --> 00:33:36.910 if your mouse has got some off-target effects and it doesn't actually affect the 543 00:33:36.910 --> 00:33:39.470 junior interest, then who cares? You know? Yeah. Uh, 544 00:33:39.570 --> 00:33:43.230 but if you are wanting to edit some cells that you are then gonna stick in your 545 00:33:43.230 --> 00:33:47.490 body, you don't want anything, you know, to be dangerous. 546 00:33:48.110 --> 00:33:49.610 So this is, I think this is, 547 00:33:49.610 --> 00:33:53.530 this is the worry that we need to be absolutely confident that the techniques 548 00:33:53.650 --> 00:33:58.330 we're gonna be doing, uh, using, which are potentially life transforming, 549 00:33:59.050 --> 00:34:03.330 assuming that they can be delivered to everybody who needs it. 550 00:34:03.330 --> 00:34:04.850 And not only to the rich. 551 00:34:05.050 --> 00:34:07.450 'cause there's also a fundamental issue of health inequalities. 552 00:34:07.450 --> 00:34:10.410 This absolutely highlights, we're back to the whole thing that, you know, 553 00:34:10.410 --> 00:34:12.610 science and medicine don't take place in a vacuum. 554 00:34:12.610 --> 00:34:16.010 They're all linked up with society. And so, you know, 555 00:34:16.030 --> 00:34:20.330 who will benefit from this? How will they benefit? But if those, 556 00:34:21.030 --> 00:34:23.810 uh, bio essential safety issues can be overcome, 557 00:34:23.990 --> 00:34:28.680 or the risk is so low that as a society and as 558 00:34:28.680 --> 00:34:32.400 individuals, we're prepared to, uh, accept those risks. Because, you know, 559 00:34:32.470 --> 00:34:36.120 lots of, every time you have a general anesthetic, it's risky, 560 00:34:36.340 --> 00:34:39.560 but we accept that risk. So it doesn't have to be a hundred percent, 561 00:34:39.640 --> 00:34:44.280 I don't think, but people have got, we as a society have to accept those risks. 562 00:34:44.580 --> 00:34:48.280 If there are any. Uh, then yeah, this can be absolutely transformational, 563 00:34:48.500 --> 00:34:50.120 not just as, uh, 564 00:34:50.360 --> 00:34:55.230 a way of altering various laboratory organisms or non laboratory 565 00:34:55.390 --> 00:34:57.230 organisms. So, as a zoologist, you know, I was, 566 00:34:57.370 --> 00:35:01.830 one of my favorite CRISPR paper from the early wave of excitement was two papers 567 00:35:02.090 --> 00:35:05.190 on ants in, in cell. Now, that's the first research, 568 00:35:05.510 --> 00:35:09.070 I think it's the only research paper cell has ever published on amp. 569 00:35:09.570 --> 00:35:13.950 But it was astonishing because it showed that, you know, if you knew a gene, uh, 570 00:35:14.330 --> 00:35:17.430 you could then manipulate it and you can deliver the, the, the, 571 00:35:17.530 --> 00:35:21.030 the CRISPR constructs to the cells that you're interested in. Uh, 572 00:35:21.300 --> 00:35:24.110 then you can change virtually any organism. 573 00:35:24.250 --> 00:35:27.150 And that from a laboratory point of view, fantastic. 574 00:35:28.390 --> 00:35:33.070 I think in terms of applications in the field, literally the fields. So, 575 00:35:33.330 --> 00:35:37.480 uh, you know, one of the most astonishing, so in writing this book, 576 00:35:37.480 --> 00:35:38.440 there are lots of stuff I didn't, 577 00:35:38.440 --> 00:35:40.720 most of the stuff I didn't know about before I started writing it. 578 00:35:41.180 --> 00:35:45.760 And the astonishing success and problems 579 00:35:45.890 --> 00:35:50.520 associated with GM crops was one of the things I found most interesting. The, 580 00:35:50.520 --> 00:35:51.353 the, the, the, 581 00:35:51.540 --> 00:35:56.400 the research by Mary De Chilton and others who enabled 582 00:35:56.420 --> 00:35:59.840 us in the eighties to be able to manipulate plants. Uh, 583 00:35:59.980 --> 00:36:02.880 and then the development of, uh, 584 00:36:05.130 --> 00:36:08.150 the two principle GM crops we have around the world, 585 00:36:08.890 --> 00:36:10.990 one of which is bt, which enables, 586 00:36:11.640 --> 00:36:15.540 makes the plant now it produces a natural insecticide. 587 00:36:15.800 --> 00:36:20.180 And that has been astonishing in terms of the reduction in the amount of 588 00:36:20.180 --> 00:36:21.980 insecticide that's been chucked around the planet. 589 00:36:22.000 --> 00:36:25.020 So whatever your problems you may or may not have about GM crops, 590 00:36:25.210 --> 00:36:30.180 that simple fact is a good thing. Uh, and that was, I mean, so Monsanto, 591 00:36:30.180 --> 00:36:31.140 which no longer exists, 592 00:36:31.160 --> 00:36:35.580 so I'm not a Monsanto shill because there's nobody to give me money, right? Uh, 593 00:36:36.280 --> 00:36:40.340 but what I was fascinated to discover that Monsanto develops that idea, 594 00:36:41.120 --> 00:36:41.370 one, 595 00:36:41.370 --> 00:36:46.260 virtually as soon as the genetic engineering of plants becomes possible in 596 00:36:46.260 --> 00:36:50.420 order, as they said, we've got to get out of pesticides, get outta chemicals, 597 00:36:50.970 --> 00:36:54.700 they at that time argued, this is not a sustainable system. 598 00:36:54.900 --> 00:36:58.740 'cause they produced, you know, uh, they produced nap arm. Uh, they, 599 00:36:59.010 --> 00:37:03.900 they produced, uh, you know, synthetic grass AstroTurf, so, you know, 600 00:37:03.900 --> 00:37:08.260 everything that was artificial they were doing. And as a company, they said, 601 00:37:08.260 --> 00:37:10.980 right, this isn't sustainable. We've gotta change this. 602 00:37:11.360 --> 00:37:16.040 We need to develop smart ways of increasing crop production. On the other hand, 603 00:37:16.040 --> 00:37:18.600 they very quickly came up with the idea of, um, 604 00:37:19.700 --> 00:37:24.430 also use making herbicide tolerant crops. So their poten, 605 00:37:24.430 --> 00:37:29.030 their, their, uh, insects, their herbicide, gly, glyphosate, 606 00:37:29.830 --> 00:37:34.120 they discovered in one of the waste pipes of one of their factories, 607 00:37:34.680 --> 00:37:39.040 a bacterium that was growing there that could resist the effects of, uh, 608 00:37:39.370 --> 00:37:42.760 glyphosate. So they then take the gene outta that, took that gene, 609 00:37:42.810 --> 00:37:46.320 stuck it into the plants. Hey, presto, we can now spray this, uh, 610 00:37:46.510 --> 00:37:49.440 herbicide everywhere. Kill all your weeds and your corn or whatever. 611 00:37:49.440 --> 00:37:52.780 It will carry on growing. Fantastic. Except, you know, uh, 612 00:37:52.780 --> 00:37:56.940 evolution is smarter than we are, and it's smarter than we are with b bt, uh, 613 00:37:56.950 --> 00:37:59.860 crops as well. And you start to get resistance strains, et cetera, et cetera. 614 00:38:00.200 --> 00:38:03.820 And so I was amazed by the ingenuity, uh, 615 00:38:04.010 --> 00:38:07.780 very surprised by the initial motivation from Monsanto researchers, 616 00:38:08.200 --> 00:38:12.060 and then also kind of slightly depressed when I discovered that the overall, 617 00:38:13.030 --> 00:38:17.970 the consequences of all this ingenuity and technology for productivity 618 00:38:18.670 --> 00:38:23.080 of crops has been no change. Yeah. So it, you know, 619 00:38:23.080 --> 00:38:26.800 we have done an amazing stuff, uh, and it is astonishing, 620 00:38:26.820 --> 00:38:29.360 and there are potentials there, but for the moment, 621 00:38:30.020 --> 00:38:33.280 it hasn't actually transformed. And part of the reason agriculture globally, 622 00:38:33.310 --> 00:38:35.220 well, it's changed it, but it hasn't transformed it. 623 00:38:35.270 --> 00:38:37.760 Part of the reason for this is that the, it's all been, 624 00:38:37.820 --> 00:38:42.360 all this research has been done on particular strains of wheat or 625 00:38:42.800 --> 00:38:44.600 whatever, uh, you know, maze. 626 00:38:44.860 --> 00:38:47.880 And those aren't necessarily the best for all circumstances. 627 00:38:47.980 --> 00:38:51.200 And this is one of the reason, in a nutshell why it hasn't, 628 00:38:51.550 --> 00:38:54.360 despite the dreams of some, uh, 629 00:38:55.390 --> 00:38:58.520 some donors and so on hasn't transformed agriculture in Africa, because, 630 00:38:58.900 --> 00:39:01.040 you know, Africa is a continent, not a country, 631 00:39:01.300 --> 00:39:05.440 and has many different ecologies and systems and ways of working, uh, 632 00:39:06.100 --> 00:39:08.520 and equally in China. So fine, I'll say on this, the, 633 00:39:08.520 --> 00:39:10.840 the most extraordinary thing I discovered was that, 634 00:39:11.180 --> 00:39:15.800 so geom crops we know 20 years ago were a real concern to people, 635 00:39:17.040 --> 00:39:21.840 I think largely because of things that had nothing to do with GM crops. 636 00:39:22.340 --> 00:39:26.000 So this was the epoch of the, the mad cow disease where, but nothing, 637 00:39:26.000 --> 00:39:29.600 nothing to do with genetics at all. But people became worried about food. 638 00:39:30.180 --> 00:39:34.920 And then there's this idea of this new food, which we're gonna use, 639 00:39:35.300 --> 00:39:39.800 and this food is got some gene from another species in it, 640 00:39:39.800 --> 00:39:43.920 and it's other stuff floating around in there too. Uh, and oh, 641 00:39:43.920 --> 00:39:46.240 I don't like the fan, don't like the sound of that. So there's, 642 00:39:46.240 --> 00:39:48.160 there's this general concern, you know, it's, 643 00:39:48.250 --> 00:39:52.960 there was the mil millennial panic about all sorts of things about, 644 00:39:53.340 --> 00:39:57.760 uh, bio terrorists, about GM crops. And a lot of that has faded now, 645 00:39:58.540 --> 00:40:01.400 but partly because, uh, in, in Europe, 646 00:40:01.460 --> 00:40:04.000 and that's still the uk despite Brexit, uh, 647 00:40:04.210 --> 00:40:08.880 there are no GM crops in the immediate human food, uh, um, 648 00:40:09.090 --> 00:40:12.800 chain, food chain. So we don't, we can't eat GM crops in Europe, 649 00:40:13.220 --> 00:40:17.040 but we do eat animals that have been fed on GM maize or whatever. 650 00:40:17.340 --> 00:40:21.960 And in America, in the us, uh, it's in the food everywhere. 651 00:40:22.060 --> 00:40:26.520 And you don't know, because you're not allowed to explicitly label saying, 652 00:40:26.830 --> 00:40:31.000 this was not made with GM crops. That's for some reason, you're not allowed to, 653 00:40:31.300 --> 00:40:34.480 the consumers aren't given that information in the us. Um, there's 654 00:40:34.620 --> 00:40:36.120 Bot technical difference here, though, isn't there, 655 00:40:36.120 --> 00:40:38.440 between GM crops and gene editing crops? 656 00:40:38.710 --> 00:40:42.640 Well, that is the hope. So, in the idea, 657 00:40:42.780 --> 00:40:45.680 and China has been one of the main powerhouses, 658 00:40:45.680 --> 00:40:47.680 this is one of the things that is really striking, 659 00:40:47.780 --> 00:40:49.920 is just as China's come to dominate the world economy, 660 00:40:50.380 --> 00:40:55.080 it has been the driving force in many areas of the application of genetic 661 00:40:55.440 --> 00:40:59.640 engineering. It was the first country to ha to grow a GM crop. GM tobacco, 662 00:40:59.890 --> 00:41:03.920 which the Americans back in the nineties said, uh, we're not gonna take this, 663 00:41:04.020 --> 00:41:04.853 uh, this, 664 00:41:04.930 --> 00:41:08.160 we're not gonna buy your tobacco crop because it is got gm and it might be 665 00:41:08.400 --> 00:41:12.240 dangerous. Uh, there you go. Uh, 666 00:41:12.420 --> 00:41:17.000 and in an indication of what has changed, China said, okay, we won't, 667 00:41:17.000 --> 00:41:20.800 we won't grow it anymore. Um, that, you know, that would never happen now. 668 00:41:20.860 --> 00:41:24.960 So China has been right from the outset, very interested in developing, uh, 669 00:41:25.160 --> 00:41:29.440 g uh, gene therapies for humans in developing new GM crops. 670 00:41:30.620 --> 00:41:34.280 But when it comes to food, when it comes to rice, 671 00:41:34.830 --> 00:41:39.320 there's been a huge yeah. Argument and rouse, and I was amazed to discover that, 672 00:41:39.460 --> 00:41:40.010 for example, 673 00:41:40.010 --> 00:41:44.560 Greenpeace is relatively free to organize in China against GM crops. 674 00:41:44.860 --> 00:41:47.880 So they have campaigns, there are demonstrations, people, you know, 675 00:41:47.880 --> 00:41:51.040 and the reason for this is that it's not only the population that's not certain 676 00:41:51.040 --> 00:41:52.960 about this, it's also the, the, 677 00:41:52.980 --> 00:41:56.800 the Chinese army leading figures in the Chinese army. I think it's all a plot, 678 00:41:56.920 --> 00:41:59.280 a western plot, to make us all sterile. So the, 679 00:41:59.280 --> 00:42:04.120 the same kind of fantasies are floating about. Now, the idea is of course, 680 00:42:04.150 --> 00:42:08.760 that okay, if we can gene edit, we can simply change one or two bases. 681 00:42:09.300 --> 00:42:10.920 And all of the, 682 00:42:11.140 --> 00:42:16.120 the apparatus that we've used to make those changes is then metabolized by 683 00:42:16.120 --> 00:42:18.040 the cells and disappears. So literally, 684 00:42:18.040 --> 00:42:22.520 you have got exactly the same results as you would've done by traditional 685 00:42:23.480 --> 00:42:26.280 mutation, selective breeding, which is how all our crops are produced. 686 00:42:27.470 --> 00:42:30.440 Then why, why should anybody complain? 687 00:42:30.830 --> 00:42:33.680 Well, it's a really interesting story here about, about the humble tomato, 688 00:42:33.930 --> 00:42:35.360 isn't it? Where, you know, 689 00:42:35.360 --> 00:42:39.880 essentially domestication tomato to make it agriculturally, um, uh, relevant, 690 00:42:39.880 --> 00:42:43.600 you know, big fruits and large plants has destroyed its taste. Yeah. 691 00:42:43.620 --> 00:42:48.240 And essentially these are made by bombarding plants with radiation or 692 00:42:48.440 --> 00:42:52.520 chemicals and creating like 20,000 mutations in a single generation and seeing 693 00:42:52.520 --> 00:42:54.040 what sticks, what, what's good here, 694 00:42:54.420 --> 00:42:56.520 and I think it was a Chinese group actually a few years ago, 695 00:42:56.520 --> 00:43:00.960 publish a paper in bio technology where they went back to the wild tomato 696 00:43:01.380 --> 00:43:04.520 and then rebuilt the good meat bottle, said, you know, the mutations, 697 00:43:04.520 --> 00:43:08.120 the agriculture, you know, relevant mutations in the wild tomato. 698 00:43:08.660 --> 00:43:12.080 And so therefore you maintain the flavor, you maintain the natural, you know, 699 00:43:12.140 --> 00:43:16.000 um, uh, uh, vitamin content of the tomato, but at the same time, 700 00:43:16.000 --> 00:43:20.080 you gave it those agriculturally relevant characteristics as well. So there, 701 00:43:20.080 --> 00:43:23.880 it's a gray area because obviously you are only giving those tomatoes something 702 00:43:23.880 --> 00:43:26.080 that's already known. Something's been tried and tested. Yeah, absolutely. 703 00:43:26.760 --> 00:43:28.420 So I think, I think that's, I mean, 704 00:43:28.420 --> 00:43:33.330 what that indicates is actually with, with, with agriculture, 705 00:43:33.630 --> 00:43:37.970 and it's clearly that psychologically there's something odd going on here. 706 00:43:38.070 --> 00:43:42.050 So let's go back to the example of, uh, insulin. You know, 707 00:43:42.880 --> 00:43:46.130 everybody who has diabetes and takes insulin, 708 00:43:46.130 --> 00:43:48.970 insulin is consuming a GM or using a GM product, 709 00:43:49.030 --> 00:43:51.090 and they're actually injecting it into their veins. 710 00:43:51.430 --> 00:43:54.290 And that doesn't seem to worry anybody. Now, 711 00:43:54.290 --> 00:43:56.850 it might be because they don't know, probably don't, 712 00:43:57.020 --> 00:44:00.530 might be because there's no alternative and there isn't really, 713 00:44:00.950 --> 00:44:04.890 or it might be because they just assume, well, medics know best, and anyway, 714 00:44:04.890 --> 00:44:05.730 this saves my life. 715 00:44:06.350 --> 00:44:11.010 But there is not the same anxiety as can be found with somebody going, oh, 716 00:44:11.030 --> 00:44:13.570 I'm not gonna eat this thing. It's weird. It's, you know, 717 00:44:13.640 --> 00:44:14.930 Franken food or whatever. 718 00:44:16.070 --> 00:44:20.890 But part of the issue with all that is actually behind in the whole 719 00:44:20.890 --> 00:44:24.170 agricultural industry is that, is that it's the, it's, you know, 720 00:44:24.170 --> 00:44:27.490 the GM crops we have have been designed to fit the industry. 721 00:44:27.490 --> 00:44:30.370 It's not the other way around. It's the mass agriculture we've got. 722 00:44:30.370 --> 00:44:32.720 It's the spraying of herbicides everywhere. 723 00:44:32.750 --> 00:44:37.640 It's the use of these very fast growing big plants 724 00:44:37.830 --> 00:44:39.320 that may not actually taste as much, 725 00:44:39.370 --> 00:44:43.960 which have been designed to meet our desire for cheaper food. Uh, 726 00:44:44.260 --> 00:44:47.560 so, you know, we are not, we're not, we as a population are not outside of this. 727 00:44:47.560 --> 00:44:50.200 We're part of it, you know, and I think there are deeper problems, 728 00:44:50.460 --> 00:44:54.600 and genetic engineering and gene editing may well be able to solve them in the 729 00:44:54.600 --> 00:44:58.160 ways you've suggested. Um, they're equally now, uh, 730 00:44:58.440 --> 00:45:00.880 tomatoes on the market which are gonna supply, uh, 731 00:45:00.880 --> 00:45:04.600 particular vitamins or particular drugs. And that, again, 732 00:45:04.780 --> 00:45:09.000 may be a way of getting people to accept that, you know, this has, 733 00:45:09.500 --> 00:45:11.840 has been done. It is, I mean, 734 00:45:11.840 --> 00:45:15.360 often the editing and scissors metaphors we use are wrong for the reasons we, 735 00:45:15.490 --> 00:45:19.240 we've explained. But I think that in some of these cases, 736 00:45:19.540 --> 00:45:23.440 it is actually true. It is simply the base pairs that have been altered, 737 00:45:23.540 --> 00:45:28.160 and you've got same result as you would've got by random 738 00:45:28.520 --> 00:45:32.920 mutation in the incredibly labor intensive ways we've been making plants for the 739 00:45:32.920 --> 00:45:35.960 last 50 years, which have fed the planet, you know? Mm-hmm. 740 00:45:35.960 --> 00:45:38.520 The green revolution has been extraordinary. That has, well, 741 00:45:38.520 --> 00:45:40.240 Of course, we, with, uh, with climate change. Well, 742 00:45:40.240 --> 00:45:43.240 there are some people saying, you know, rather than, rather than the argument, 743 00:45:43.240 --> 00:45:45.320 let's slow down climate change, people are saying, 744 00:45:45.450 --> 00:45:47.400 let's adapt our crops to accommodate. 745 00:45:47.600 --> 00:45:50.320 Well, we're gonna have to, because, you know, things are, 746 00:45:50.320 --> 00:45:51.160 the weather's changing, 747 00:45:51.300 --> 00:45:55.200 so we're going to need crops that can resist desiccation, uh, you know, 748 00:45:55.200 --> 00:45:57.280 periods of, uh, long periods of drought, 749 00:45:57.660 --> 00:46:00.280 and there are genes around that do that. 750 00:46:00.420 --> 00:46:03.600 And so I think those kind of ways, uh, 751 00:46:04.370 --> 00:46:08.520 maybe a way of, yeah. I mean, it's very interesting. 752 00:46:08.520 --> 00:46:11.920 The Chinese researchers who are involved in this are very insistent that there 753 00:46:11.920 --> 00:46:14.720 isn't gonna be a magic bullet. And I think we've always gotta, okay, 754 00:46:14.720 --> 00:46:17.400 we can all do this, and it's going to be, uh, you know, new, 755 00:46:17.580 --> 00:46:21.480 new plants to meet climate change, to meet new medical needs, 756 00:46:21.500 --> 00:46:23.360 or simply to increase. 757 00:46:23.470 --> 00:46:27.120 Varieties are going to come about through a whole series of ways, you know, 758 00:46:27.480 --> 00:46:30.120 selective breeding mutation, gene editing, 759 00:46:30.380 --> 00:46:33.960 and we're gonna have to need all those different techniques. But this is, 760 00:46:34.110 --> 00:46:38.320 this is very real, I think, uh, in terms of what the future holds. And it, it, 761 00:46:38.320 --> 00:46:43.200 it's not kind of fantasies about making photosynthesis more effective. I mean, 762 00:46:43.200 --> 00:46:46.640 you know, you, you don't need to, that may happen, but, you know, 763 00:46:46.640 --> 00:46:51.560 there are more immediate ways of altering our plants to make 764 00:46:51.560 --> 00:46:56.510 them resist climate change disease. It's very striking. 765 00:46:56.540 --> 00:47:00.150 There's only a handful of GM crops resist disease. 766 00:47:00.900 --> 00:47:02.590 It's very odd. And I, I I, 767 00:47:02.750 --> 00:47:06.990 I generally don't know whether this is because it's hellishly difficult or 768 00:47:06.990 --> 00:47:10.670 because there's not as much money in it. Uh, and you know, we're caught up in a, 769 00:47:11.030 --> 00:47:15.870 a system which is both extraordinary. There are things I'm worried about. 770 00:47:16.230 --> 00:47:18.270 I mean, we talked at the beginning about anxieties, 771 00:47:18.330 --> 00:47:22.790 and what I'm fascinated by is that those anxieties keep on recurring. 772 00:47:23.490 --> 00:47:25.230 Uh, I am worried about some things, 773 00:47:25.330 --> 00:47:29.720 but they are to do with the edge of this technology. 774 00:47:30.180 --> 00:47:34.760 Uh, and it's not GM crops. It's, uh, you know, gain of function studies, 775 00:47:34.760 --> 00:47:39.200 which I'm concerned about. It's not editing a cure disease. 776 00:47:39.510 --> 00:47:43.440 It's the, what we have already seen with her John Key. It's the use of, 777 00:47:43.710 --> 00:47:48.160 it's the, the pointless, I would argue, uh, embryo editing, 778 00:47:48.440 --> 00:47:51.840 germline editing. There's no need to do that. It's just only benefit. 779 00:47:51.840 --> 00:47:56.320 Even they all now admit all the various research groups and ethical groups that 780 00:47:56.320 --> 00:47:59.680 this would only benefit a few, you know, a tiny minority, 781 00:47:59.710 --> 00:48:02.920 literally a few hundred people around the world could benefit from that. 782 00:48:03.260 --> 00:48:04.280 And finally, that's a 783 00:48:04.280 --> 00:48:06.560 Great example of self-regulation though, isn't it? Yeah, absolutely. 784 00:48:06.560 --> 00:48:09.880 Obviously a terrible incident there. But straight away, the, the, uh, the, 785 00:48:09.880 --> 00:48:14.280 the Royal Academy, I believe, um, um, and the national, um, um, uh, 786 00:48:14.720 --> 00:48:18.760 n n I h got together post report saying this is not good. You know, 787 00:48:18.820 --> 00:48:20.560 so that sort regulation came into practice. 788 00:48:21.230 --> 00:48:24.440 Yeah. And the, the final element, which we haven't talked about all, 789 00:48:24.440 --> 00:48:26.920 but I kind of vaguely hinted at, is the idea of gene drive. 790 00:48:26.940 --> 00:48:30.440 So this is releasing self-replicating, uh, 791 00:48:30.470 --> 00:48:35.360 rapidly exploding, uh, genes into pest populations, 792 00:48:35.380 --> 00:48:38.400 say mosquitoes, uh, which on the one hand looks like, well, 793 00:48:38.400 --> 00:48:39.120 why wouldn't you want to do that? 794 00:48:39.120 --> 00:48:43.400 Because you can get rid of mosquitoes in a malaria ridden area. But, you know, 795 00:48:44.040 --> 00:48:47.080 mosquitoes move. And so the, but again, 796 00:48:47.100 --> 00:48:51.550 the scientists involved have been the first people to say, Hey, 797 00:48:51.550 --> 00:48:56.270 this is scary. I mean, the first publication of actually showing it worked, 798 00:48:56.530 --> 00:48:59.910 uh, talked to, basically used the same language of saying, 799 00:48:59.910 --> 00:49:03.470 we've created a genetic bomb, which they had, uh, you know, this is a, 800 00:49:03.770 --> 00:49:07.350 so I think, I don't think there's any reason to be complacent. Um, 801 00:49:07.670 --> 00:49:12.280 I think there's lots of reasons to be excited, but like any technology, 802 00:49:12.780 --> 00:49:17.120 uh, you've got to develop the, the, 803 00:49:17.300 --> 00:49:20.880 the regulation around it. I mean, let's go back to the railways. You know, 804 00:49:20.880 --> 00:49:25.480 the railways changed the world and were, 805 00:49:26.100 --> 00:49:29.720 uh, both terrifying and very, you know, create great anxieties, 806 00:49:29.750 --> 00:49:32.400 lots of Victorian novels about railways, 807 00:49:32.900 --> 00:49:35.400 and they ended up with a system which is pretty safe. I mean, 808 00:49:35.400 --> 00:49:39.680 we do have railway accidents, but as, as railway workers say that, 809 00:49:39.680 --> 00:49:43.280 that the safety regulations are written in blood because there were accidents, 810 00:49:43.280 --> 00:49:47.120 and so they learnt about how to make the signal safer or whatever. Um, 811 00:49:47.450 --> 00:49:49.800 we've gotta avoid that. I think the genetic engineering, 812 00:49:49.800 --> 00:49:52.240 we haven't had that kind of accident. 813 00:49:52.240 --> 00:49:57.120 There hasn't been anything terrible has happened yet, apart from a junkie. Um, 814 00:49:57.940 --> 00:50:00.680 but there's been nothing on a mass scale, and let's keep it that way. 815 00:50:00.740 --> 00:50:05.360 But the way you do that is by being worried and not by dismissing concerns as, 816 00:50:05.360 --> 00:50:07.000 okay, what's the same arguments as ever? 817 00:50:07.300 --> 00:50:09.280 How do they apply to these new developments? 818 00:50:09.620 --> 00:50:14.080 How can we ensure that there is effective regulation and also, uh, 819 00:50:14.160 --> 00:50:17.400 exploitation development of new therapies, foods, 820 00:50:18.210 --> 00:50:21.240 scientific discoveries, whatever it is, uh, 821 00:50:21.460 --> 00:50:23.640 within a framework that we can employ safely. 822 00:50:25.010 --> 00:50:28.160 Matthew, it's been absolutely fascinating. Um, I think we have to end there, 823 00:50:28.340 --> 00:50:30.440 but, well, wonderful. It's been great conversation today. 824 00:50:30.440 --> 00:50:31.480 Thank you so much for joining me. 825 00:50:32.140 --> 00:50:35.370 Thank you very much. I, I hope listeners have found it interesting. 826 00:50:36.500 --> 00:50:40.560 You've been listening to CRISPR Unedited. To access more thoughts, 827 00:50:40.630 --> 00:50:42.200 help and advice on crispr, 828 00:50:42.290 --> 00:50:47.280 visit bitesize bio.com/crispr-unedited.