WEBVTT 00:00:01.066 --> 00:00:03.527 So this is a talk about gene drives, 00:00:03.527 --> 00:00:06.801 but I'm going to start by telling you a brief story. 00:00:06.801 --> 00:00:09.868 20 years ago, a biologist named Anthony James 00:00:09.868 --> 00:00:12.211 got obsessed with the idea of making mosquitos 00:00:12.211 --> 00:00:15.857 that didn't transmit malaria. NOTE Paragraph 00:00:15.857 --> 00:00:20.803 It was a great idea, and pretty much a complete failure. 00:00:20.803 --> 00:00:23.427 For one thing, it turned out to be really hard 00:00:23.427 --> 00:00:26.469 to make a malaria resistant mosquito. 00:00:26.469 --> 00:00:29.536 James managed it, finally, just a few years ago 00:00:29.536 --> 00:00:31.902 by adding some genes that make it impossible 00:00:31.902 --> 00:00:35.757 for the malaria parasite to survive inside the mosquito. NOTE Paragraph 00:00:35.757 --> 00:00:38.218 But that just created another problem. 00:00:38.218 --> 00:00:41.051 Now that you've got a malaria-resistant mosquito, 00:00:41.051 --> 00:00:46.322 how do you get it to replace all the malaria-carrying mosquitos? 00:00:46.322 --> 00:00:48.133 There are a couple options, 00:00:48.133 --> 00:00:50.009 but plan A was basically to breed up 00:00:50.009 --> 00:00:52.459 a bunch of the new genetically-engineered mosquitos 00:00:52.459 --> 00:00:54.263 release them into the wild, 00:00:54.263 --> 00:00:56.673 and hope that they pass on their genes. 00:00:56.673 --> 00:00:58.811 The problem was that you'd have to release 00:00:58.811 --> 00:01:03.135 literally 10x the number of native mosquitos to work. 00:01:03.135 --> 00:01:05.246 So in a village with 10,000 mosquitos, 00:01:05.246 --> 00:01:08.497 you release an extra 100,000. 00:01:08.497 --> 00:01:11.004 As you might guess, this was not a very popular strategy 00:01:11.004 --> 00:01:12.514 with the villagers. 00:01:12.514 --> 00:01:15.137 (Laughter) NOTE Paragraph 00:01:15.137 --> 00:01:18.829 Then, last January, Anthony James got an email 00:01:18.829 --> 00:01:21.639 from a biologist named Ethan Bier. 00:01:21.639 --> 00:01:24.272 Bier said that he and his grad student, Valentino Gantz, 00:01:24.272 --> 00:01:26.887 had stumbled on a tool that could not only guarentee 00:01:26.887 --> 00:01:30.161 that a particular genetic trait would be inherited, 00:01:30.161 --> 00:01:32.354 but that it would spread incredibly quickly. 00:01:32.354 --> 00:01:35.223 If they were right, it would basically solve the problem 00:01:35.223 --> 00:01:38.752 that he and James had been working on for 20 years. NOTE Paragraph 00:01:38.752 --> 00:01:41.562 As a test, they engineered two mosquitos 00:01:41.562 --> 00:01:43.257 to carry the anti-malaria gene 00:01:43.257 --> 00:01:45.556 and also this new tool, a gene drive, 00:01:45.556 --> 00:01:47.506 which I'll explain in a minute. 00:01:47.506 --> 00:01:49.712 Finally, they set it up so that any mosquitos 00:01:49.712 --> 00:01:51.825 that had inherited the anti-malaria gene 00:01:51.825 --> 00:01:55.585 wouldn't have the usual white eyes, but would instead have red eyes. 00:01:55.585 --> 00:01:58.280 That was pretty much just for convenience 00:01:58.280 --> 00:02:02.413 so they could tell just at a glance which was which. NOTE Paragraph 00:02:02.413 --> 00:02:05.153 So they took their two anti-malarial, red-eyed mosquitos 00:02:05.153 --> 00:02:07.847 and put them in a box with 30 ordinary white-eyed ones 00:02:07.847 --> 00:02:09.797 and let them breed. 00:02:09.797 --> 00:02:14.534 In two generations, those had produced 38,000 grandchildren. 00:02:14.534 --> 00:02:16.972 That is not the surprising part. 00:02:16.972 --> 00:02:18.923 This is the surprising part: 00:02:18.923 --> 00:02:21.593 Given that you started with just two red-eyed mosquitos 00:02:21.593 --> 00:02:23.172 and 30 white-eyed ones, 00:02:23.172 --> 00:02:26.725 you expect mostly white-eyed descendents. 00:02:26.725 --> 00:02:29.790 Instead, when James opened the box, 00:02:29.790 --> 00:02:33.598 all 38,000 mosquitos had red eyes. NOTE Paragraph 00:02:33.598 --> 00:02:35.822 When I asked Ethan Bier about this moment, 00:02:35.822 --> 00:02:39.723 he became so excited, tht he was literally shouting into the phone. 00:02:39.723 --> 00:02:42.073 That's because getting only red-eyed mosquitos 00:02:42.073 --> 00:02:45.045 violates a rule that is the absolute cornerstone of biology, 00:02:45.045 --> 00:02:46.912 Mendelian genetics. 00:02:46.912 --> 00:02:49.202 I'll keep this quick, but Mendelian genetics 00:02:49.202 --> 00:02:50.873 says when a male and a female mate, 00:02:50.873 --> 00:02:53.753 their baby inherits half of its DNA from each parent. 00:02:53.753 --> 00:02:57.352 So if our original mosquito was aa and our new mosquito is aB, 00:02:57.352 --> 00:02:59.140 where B is the anti-malarial gene, 00:02:59.140 --> 00:03:01.415 the babies should come out in four permutations: 00:03:01.415 --> 00:03:05.130 aa, aB, aa, Ba. 00:03:05.130 --> 00:03:07.197 Instead, with the new gene drive, 00:03:07.197 --> 00:03:10.123 they all came out aB. 00:03:10.123 --> 00:03:12.723 Biologically, that shouldn't even be possible. NOTE Paragraph 00:03:12.723 --> 00:03:14.906 So what happened? 00:03:14.906 --> 00:03:17.197 The first thing that happened was the arrival 00:03:17.197 --> 00:03:20.055 of a gene-editing tool known as CRISPR in 2012. 00:03:20.055 --> 00:03:22.538 Many of you have probably heard about CRISPR, 00:03:22.538 --> 00:03:25.831 so I'll just say briefly that CRISPR is a tool that allows researchers 00:03:25.831 --> 00:03:29.038 to edit genes very precisely, easily and quickly. 00:03:29.038 --> 00:03:32.712 It does this by harnessing a mechanism that already existed in bacteria. 00:03:32.712 --> 00:03:35.409 Basically, there's a protein that acts like a scissors 00:03:35.409 --> 00:03:36.877 and cuts the DNA, 00:03:36.877 --> 00:03:39.427 and there's an RNA molecule that directs the scissors 00:03:39.427 --> 00:03:41.237 to any point on the genome you want. 00:03:41.237 --> 00:03:44.651 The result is basically a word processor word processor for genes. 00:03:44.651 --> 00:03:47.135 You can take an entire gene out, put one in, 00:03:47.135 --> 00:03:49.945 or even edit just a single letter within a gene. 00:03:49.945 --> 00:03:53.544 And you can do it in nearly any species. NOTE Paragraph 00:03:53.544 --> 00:03:55.641 Okay, remember how I said that gene drives 00:03:55.641 --> 00:03:57.914 originally had two problems? 00:03:57.914 --> 00:04:01.137 The first was that it was hard to engineer a mosquito 00:04:01.137 --> 00:04:02.623 to be malaria resistant. 00:04:02.623 --> 00:04:05.363 That's basically gone now, thanks to CRISPR. 00:04:05.363 --> 00:04:07.546 But the other problem was logistical. 00:04:07.546 --> 00:04:10.402 How do you get your trait to spread? 00:04:10.402 --> 00:04:13.165 This is where it gets clever. NOTE Paragraph 00:04:13.165 --> 00:04:16.450 A couple years ago, a biologist at Harvard named Kevin Esvelt 00:04:16.450 --> 00:04:18.986 wondered what would happen if you made it so that 00:04:18.986 --> 00:04:21.803 CRISPR inserted not only your new gene, 00:04:21.803 --> 00:04:25.448 but also the machinery that does the cutting and pasting. 00:04:25.448 --> 00:04:30.185 In other words, what if CRISPR also copy and pasted itself. 00:04:30.185 --> 00:04:34.713 You'd end up with a perpetual motion machine for gene editing. 00:04:34.713 --> 00:04:37.267 And that's exactly what happened. 00:04:37.267 --> 00:04:40.077 This CRISPR gene drive that Esvelt created 00:04:40.077 --> 00:04:43.606 not only guarantees that a trait will get passed on, 00:04:43.606 --> 00:04:46.068 but if its used in the germline cell, 00:04:46.068 --> 00:04:48.668 it will automatically copy and paste your new gene 00:04:48.668 --> 00:04:51.989 into both chromosomes of every single individual. 00:04:51.989 --> 00:04:54.450 It's like a global search and replace, 00:04:54.450 --> 00:04:58.666 or in science terms, it makes a heterozygous trait homozygous. NOTE Paragraph 00:04:58.666 --> 00:05:01.927 So, what does this mean? 00:05:01.927 --> 00:05:04.574 For one thing, it means we have a very powerful, 00:05:04.574 --> 00:05:08.576 but also somewhat alarming new tool. 00:05:08.576 --> 00:05:11.586 Up until now, the fact that gene drives didn't work very well 00:05:11.586 --> 00:05:13.269 was actually kind of a relief. 00:05:13.269 --> 00:05:15.898 Normally when we mess around with an organisms's genes, 00:05:15.898 --> 00:05:18.264 we make that thing less evolutionarily fit. 00:05:18.264 --> 00:05:21.264 So biologists can make all the mutant fruit flies they want 00:05:21.264 --> 00:05:22.500 without worrying about it. 00:05:22.500 --> 00:05:27.004 If some escape, natural selection just takes care of it. NOTE Paragraph 00:05:27.004 --> 00:05:30.302 What's remarkable and powerful and frightening about gene drives 00:05:30.302 --> 00:05:32.856 is that that will no longer be true. 00:05:32.856 --> 00:05:36.943 Assuming that your trait does not have a big evolutionary handicap, 00:05:36.943 --> 00:05:39.009 like a mosquito that can't fly, 00:05:39.009 --> 00:05:42.492 the CRISPR-based gene drive will spread the change relentlessly 00:05:42.492 --> 00:05:47.322 until it is in every single individual in the population. 00:05:47.322 --> 00:05:50.178 Now, it isn't easy to make a gene drive that works that well, 00:05:50.178 --> 00:05:53.568 but James and Esvelt think that we can. NOTE Paragraph 00:05:53.568 --> 00:05:57.469 The good news is that this opens the door to some remarkable things. 00:05:57.469 --> 00:06:00.116 If you put an anti-malarial gene drive in just 1 percent 00:06:00.116 --> 00:06:03.143 of anopheles mosquitos, the species that transmits malaria. 00:06:03.143 --> 00:06:06.502 Researchers estimate that it would spread to the entire population 00:06:06.502 --> 00:06:08.406 in a year. 00:06:08.406 --> 00:06:11.071 So in a year, you could virtually eliminate malaria. 00:06:11.071 --> 00:06:14.350 In practice, we're still a few years out from being able to do that, 00:06:14.350 --> 00:06:18.344 but sitll, a 1,000 children a day die of malaria. 00:06:18.344 --> 00:06:21.293 In a year, that number could be almost zero. 00:06:21.293 --> 00:06:25.426 The same goes for dengue fever, chicken genuang (?), yellow fever. NOTE Paragraph 00:06:25.426 --> 00:06:27.469 And it gets better. 00:06:27.469 --> 00:06:30.022 Say you want to get rid of an invasive species, 00:06:30.022 --> 00:06:32.670 like get Asian Carp out of The Great Lakes. 00:06:32.670 --> 00:06:34.692 All you have to do is release a gene drive 00:06:34.692 --> 00:06:37.570 that makes the fish produce only male offspring. 00:06:37.570 --> 00:06:41.419 In a few generations, there'll be no females left, no more carp. 00:06:41.419 --> 00:06:44.164 In theory, this means that we could restore hundreds 00:06:44.164 --> 00:06:47.601 of native species that have been pushed to the brink. NOTE Paragraph 00:06:47.601 --> 00:06:50.968 Okay, that's the good news, 00:06:50.968 --> 00:06:53.313 this is the bad news. 00:06:53.313 --> 00:06:55.380 Gene drives are so effective, 00:06:55.380 --> 00:06:59.234 that even an accidental release could change an entire species, 00:06:59.234 --> 00:07:01.440 and often very quickly. 00:07:01.440 --> 00:07:03.530 Anthony James took good precautions. 00:07:03.530 --> 00:07:05.746 He breed his mosquitos in a bio-containment lab 00:07:05.746 --> 00:07:08.427 and he also used a species that's not native to the US 00:07:08.427 --> 00:07:10.176 so that even if some did escape, 00:07:10.176 --> 00:07:11.494 they'd just die off, 00:07:11.494 --> 00:07:13.515 there'd be nothing for them to mate with. 00:07:13.515 --> 00:07:15.651 But it's also true that if a dozen Asian Carp 00:07:15.651 --> 00:07:19.482 with the all-male gene drive accidentally got carried from The Great Lakes 00:07:19.482 --> 00:07:20.968 back to Asia, 00:07:20.968 --> 00:07:25.519 they could potentially wipe out the native Asian Carp population. 00:07:25.519 --> 00:07:29.048 And that's not so unlikely, given how connected our world is. 00:07:29.048 --> 00:07:32.230 In fact, it's why we have an invasive species problem. 00:07:32.230 --> 00:07:33.646 And that's fish. 00:07:33.646 --> 00:07:37.826 Things like mosquitos and fruit flies, there's literally no way to contain them. 00:07:37.826 --> 00:07:41.982 They cross borders and oceans all the time. NOTE Paragraph 00:07:41.982 --> 00:07:44.467 Okay, the other piece of bad news is that 00:07:44.467 --> 00:07:48.139 a gene drive might not stay confined to what we call the target species. 00:07:48.139 --> 00:07:50.079 That's because of gene flow, 00:07:50.079 --> 00:07:52.874 which is a fancy way of saying that neighboring species 00:07:52.874 --> 00:07:54.103 sometimes inter-breed. 00:07:54.103 --> 00:07:57.147 If that happens, it's possible a gene drive could cross over, 00:07:57.147 --> 00:07:59.861 like Asian Carp could infect some other kind of Carp. 00:07:59.861 --> 00:08:03.437 That's not so bad if your drive just promotes a trait, like eye color. 00:08:03.437 --> 00:08:06.372 In fact, there's a decent chance that we'll see a wave 00:08:06.372 --> 00:08:09.614 of very weird fruit flies in the near future. 00:08:09.614 --> 00:08:12.353 But it could be a disaster if your drive is deigned 00:08:12.353 --> 00:08:14.629 to eliminate the species entirely. NOTE Paragraph 00:08:14.629 --> 00:08:17.903 The last worrisome thing is that the technology to do this, 00:08:17.903 --> 00:08:21.618 to genetically engineer an organism and include a gene drive, 00:08:21.618 --> 00:08:25.543 is something that basically any lab in the world can do. 00:08:25.543 --> 00:08:27.423 An undergraduate can do it. 00:08:27.423 --> 00:08:32.160 A talented high schooler with some equipment can do it. NOTE Paragraph 00:08:32.160 --> 00:08:35.527 Now I'm guessing that this sounds terrifying. 00:08:35.527 --> 00:08:40.495 Interestingly though, nearly every scientist I talk to 00:08:40.495 --> 00:08:43.097 seems to think that gene drives were not actually 00:08:43.097 --> 00:08:44.583 that frightening or dangerous. 00:08:44.583 --> 00:08:47.072 Partly because they believe that scientists will be 00:08:47.072 --> 00:08:49.444 very cautious and responsible about using them. 00:08:49.444 --> 00:08:50.318 (Laughter) 00:08:50.318 --> 00:08:52.524 So far, that's been true. NOTE Paragraph 00:08:52.524 --> 00:08:55.380 But gene drives also have some actual limitations. 00:08:55.380 --> 00:08:58.399 For one thing, they work in only sexually reproducing species. 00:08:58.399 --> 00:09:01.882 So thank goodness, they can't be used to engineer viruses or bacteria. 00:09:01.882 --> 00:09:05.243 Also, the trait spreads only with each succesive genertion. 00:09:05.243 --> 00:09:08.732 So changing or eliminating a population is practical only if that species 00:09:08.732 --> 00:09:11.100 has a fast reproductive cycle, 00:09:11.100 --> 00:09:14.192 like insects or maybe small vertebrates like mice or fish. 00:09:14.192 --> 00:09:16.534 In elephants or people, it would take centuries 00:09:16.534 --> 00:09:20.342 for a trait to spread widely enough to matter. NOTE Paragraph 00:09:20.342 --> 00:09:25.492 Also, even with CRISPR, it's not that easy to engineer a truly devastating trait. 00:09:25.492 --> 00:09:27.679 Say you wanted to make a fruit fly 00:09:27.679 --> 00:09:30.303 that feeds on ordinary fruit instead of rotting fruit 00:09:30.303 --> 00:09:33.068 with the aim of sabotaging American agriculture. 00:09:33.068 --> 00:09:35.481 First you'd have to figure out which genes control 00:09:35.481 --> 00:09:37.594 what the fly wants to eat, 00:09:37.594 --> 00:09:40.636 which is already a very long and complicated project. 00:09:40.636 --> 00:09:43.817 Then you'd have to alter those genes to change the fly's behavior 00:09:43.817 --> 00:09:45.442 to whatever you'd want it to be, 00:09:45.442 --> 00:09:48.087 which is an even longer and more complicated project. 00:09:48.087 --> 00:09:49.807 And it might not even work because 00:09:49.807 --> 00:09:52.024 the genes that control behavior are complex. 00:09:52.024 --> 00:09:54.591 So if you're a terrorist and have to choose between 00:09:54.591 --> 00:09:56.222 starting a grueling basic research program 00:09:56.222 --> 00:09:57.726 that will require years of meticulous lab work 00:09:57.726 --> 00:09:59.398 and still might not pan out, 00:09:59.398 --> 00:10:00.768 or just blowing stuff up? 00:10:00.768 --> 00:10:03.237 You'll probably choose the later. NOTE Paragraph 00:10:03.237 --> 00:10:05.621 This is especially true because at least in theory, 00:10:05.621 --> 00:10:09.011 it should be pretty easy to build what's called a reversal drive. 00:10:09.011 --> 00:10:13.028 That's one that basically overwrites the change made by the first gene drive. 00:10:13.028 --> 00:10:15.303 So if you don't like the effects of a change, 00:10:15.303 --> 00:10:18.159 you can just release a second drive that will cancel it out, 00:10:18.159 --> 00:10:21.573 at least in theory. NOTE Paragraph 00:10:21.573 --> 00:10:24.847 Okay, so where does this leave us? 00:10:24.847 --> 00:10:29.351 We now have the ability to change entire species at will. 00:10:29.351 --> 00:10:30.814 Should we? 00:10:30.814 --> 00:10:34.251 Are we gods now? 00:10:34.251 --> 00:10:36.317 I'm not sure I'd say that. 00:10:36.317 --> 00:10:38.663 But I would say this: 00:10:38.663 --> 00:10:41.426 First, some very smart people are even now debating 00:10:41.426 --> 00:10:43.841 how to regulate gene drives. 00:10:43.841 --> 00:10:46.418 At the same time, some other very smart people 00:10:46.418 --> 00:10:48.601 are working hard to create safeguards, 00:10:48.601 --> 00:10:52.177 like gene drives that self regulate or petter out after a few generations. 00:10:52.177 --> 00:10:53.427 That's great. 00:10:53.427 --> 00:10:56.471 But this technology still requires a conversation. 00:10:56.471 --> 00:10:59.723 And given the nature of gene drives, 00:10:59.723 --> 00:11:02.370 that conversation has to be global. 00:11:02.370 --> 00:11:05.528 What if Kenya wants to use a drive that Tanzania doesn't? 00:11:05.528 --> 00:11:09.557 Who decides whether to release a gene drive that can fly? NOTE Paragraph 00:11:11.287 --> 00:11:13.841 I don't have the answer to that question. 00:11:13.841 --> 00:11:15.884 All we can do going forward, I think, 00:11:15.884 --> 00:11:18.671 is talk honestly about the risks and benefits 00:11:18.671 --> 00:11:21.945 and take responsibility for our choices. 00:11:21.945 --> 00:11:25.962 By that I mean, not just the choice to use a gene drive, 00:11:25.962 --> 00:11:29.421 but also the choice not to use one. 00:11:29.421 --> 00:11:32.347 Humans have a tendency to assume that the safest option 00:11:32.347 --> 00:11:35.064 is to preserve the status quo. 00:11:35.064 --> 00:11:37.711 But that's not always the case. 00:11:37.711 --> 00:11:41.356 Gene drives have risks and those need to be discussed, 00:11:41.356 --> 00:11:45.211 but malaria exists now and kills 1,000 people a day. 00:11:45.211 --> 00:11:48.856 To combat it, we spray pesticides that do grave damage to other species, 00:11:48.856 --> 00:11:51.605 including amphibians and birds. 00:11:51.605 --> 00:11:54.336 So when you hear about gene drives in the coming months, 00:11:54.336 --> 00:11:57.193 and trust me, you will be hearing about them, 00:11:57.193 --> 00:11:58.632 remember that. 00:11:58.632 --> 00:12:00.675 It can be frightening to act, 00:12:00.675 --> 00:12:04.925 but sometimes, not acting is worse. NOTE Paragraph 00:12:04.925 --> 00:12:07.948 (Applause)