1 99:59:59,999 --> 99:59:59,999 So this is a talk about gene drives, 2 99:59:59,999 --> 99:59:59,999 but I'm going to start by telling you a brief story. 3 99:59:59,999 --> 99:59:59,999 20 years ago, a biologist named Anthony James 4 99:59:59,999 --> 99:59:59,999 got obsessed by the idea of making mosquitos 5 99:59:59,999 --> 99:59:59,999 that didn't transmit malaria. 6 99:59:59,999 --> 99:59:59,999 It was a great idea, but pretty much a complete failure. 7 99:59:59,999 --> 99:59:59,999 For one thing, it turned out to be really hard 8 99:59:59,999 --> 99:59:59,999 to make a malaria resistant mosquito. 9 99:59:59,999 --> 99:59:59,999 James managed it, finally, just a few years ago 10 99:59:59,999 --> 99:59:59,999 by adding some genes that make it impossible 11 99:59:59,999 --> 99:59:59,999 for the malaria gene to survive inside the mosquito. 12 99:59:59,999 --> 99:59:59,999 But that just created another problem. 13 99:59:59,999 --> 99:59:59,999 Now that you've got malaria-resistant mosquito, 14 99:59:59,999 --> 99:59:59,999 how do you get it to replace all the malaria-carrying mosquitos? 15 99:59:59,999 --> 99:59:59,999 There are a couple options, 16 99:59:59,999 --> 99:59:59,999 but plan A was basically to breed up a bunch of the new genetically-engineered mosquotos, 17 99:59:59,999 --> 99:59:59,999 release them into the wild, 18 99:59:59,999 --> 99:59:59,999 and hope that they pass on their genes. 19 99:59:59,999 --> 99:59:59,999 The problem was that you'd have to release 20 99:59:59,999 --> 99:59:59,999 literally 10x the number of native mosquitos to work. 21 99:59:59,999 --> 99:59:59,999 So in a village with 10,000 mosquitos, 22 99:59:59,999 --> 99:59:59,999 you release an extra 100,000. 23 99:59:59,999 --> 99:59:59,999 As you might guess, this was not a very popular strategy 24 99:59:59,999 --> 99:59:59,999 with the villagers. 25 99:59:59,999 --> 99:59:59,999 (Laughter) 26 99:59:59,999 --> 99:59:59,999 Then, last January, Anthony James got an email 27 99:59:59,999 --> 99:59:59,999 from a biologist named Ethan Bier. 28 99:59:59,999 --> 99:59:59,999 Bier said that he and his grad student, Valentino Gantz, 29 99:59:59,999 --> 99:59:59,999 had stumbled on a tool that could not only guarentee 30 99:59:59,999 --> 99:59:59,999 that a particular gene trait would not be inherited, 31 99:59:59,999 --> 99:59:59,999 but that it would spread incredibly quickly. 32 99:59:59,999 --> 99:59:59,999 If they were right, it would basically solve the problem 33 99:59:59,999 --> 99:59:59,999 that he and James had been working on for 20 years. 34 99:59:59,999 --> 99:59:59,999 As a test, they engineered two mosquitos 35 99:59:59,999 --> 99:59:59,999 to carry the anti-malaria gene 36 99:59:59,999 --> 99:59:59,999 and also this new tool, a gene drive, 37 99:59:59,999 --> 99:59:59,999 which I'll explain in a minute. 38 99:59:59,999 --> 99:59:59,999 Finally, they set it up so that any mosquitos 39 99:59:59,999 --> 99:59:59,999 that had inherited the anti-malaria gene 40 99:59:59,999 --> 99:59:59,999 wouldn't have the usual white eyes, but would instead have red eyes. 41 99:59:59,999 --> 99:59:59,999 That was pretty much just for convenience 42 99:59:59,999 --> 99:59:59,999 so they could tell just at a glance which was which. 43 99:59:59,999 --> 99:59:59,999 So they took their two anti-malarial, red eye mosquitos 44 99:59:59,999 --> 99:59:59,999 and put them in a box with 30 ordinary white-eyed ones 45 99:59:59,999 --> 99:59:59,999 and let them breed. 46 99:59:59,999 --> 99:59:59,999 In two generations, those had produced 38,000 grandchildren. 47 99:59:59,999 --> 99:59:59,999 That is not the surprising part. 48 99:59:59,999 --> 99:59:59,999 This is the surprising part: 49 99:59:59,999 --> 99:59:59,999 given that you started with just two red-eyed mosquitos 50 99:59:59,999 --> 99:59:59,999 and 30 white-eyed ones, 51 99:59:59,999 --> 99:59:59,999 you expect mostly white-eyed descendents. 52 99:59:59,999 --> 99:59:59,999 Instead, when James opened the box, 53 99:59:59,999 --> 99:59:59,999 all 38,000 mosquitos had red eyes. 54 99:59:59,999 --> 99:59:59,999 When I asked Ethan Bier about this moment, 55 99:59:59,999 --> 99:59:59,999 he became so excited, tht he was literally shouting into the phone. 56 99:59:59,999 --> 99:59:59,999 That's because getting only red-eyed mosquitos 57 99:59:59,999 --> 99:59:59,999 violates a rule that is the absolute cornerstone of biology, 58 99:59:59,999 --> 99:59:59,999 Mendelian genetics. 59 99:59:59,999 --> 99:59:59,999 I'll keep this quick, but Mendelian genetics says when a male and female mate, 60 99:59:59,999 --> 99:59:59,999 their baby inherits half of its DNA from each parent. 61 99:59:59,999 --> 99:59:59,999 So if our original mosquito was aa and our new mosquito is aB, 62 99:59:59,999 --> 99:59:59,999 where B is the anti-malarial gene, 63 99:59:59,999 --> 99:59:59,999 the babies should come out in four permutations: 64 99:59:59,999 --> 99:59:59,999 aa, aB, aa and Ba. 65 99:59:59,999 --> 99:59:59,999 Instead, with the new gene drive, 66 99:59:59,999 --> 99:59:59,999 they all came out aB. 67 99:59:59,999 --> 99:59:59,999 Biologically, that shouldn't even be possible. 68 99:59:59,999 --> 99:59:59,999 So what happened? 69 99:59:59,999 --> 99:59:59,999 The first thing that happened was the arrival 70 99:59:59,999 --> 99:59:59,999 of a gene-editing tool known as CRISPR in 2012. 71 99:59:59,999 --> 99:59:59,999 Many of you have probably heard about CRISPR, 72 99:59:59,999 --> 99:59:59,999 so I'll just say briefly that CRISPR is a tool that allows researchers 73 99:59:59,999 --> 99:59:59,999 to edit genes very precisely, easily and quickly. 74 99:59:59,999 --> 99:59:59,999 It does this by harnessing a mechanism that already existed in bacteria. 75 99:59:59,999 --> 99:59:59,999 Basically, there's a protein that acts like a scissors 76 99:59:59,999 --> 99:59:59,999 and cuts the DNA, 77 99:59:59,999 --> 99:59:59,999 and there's an RNA molecule that directs the scissors 78 99:59:59,999 --> 99:59:59,999 to any point on the genome you want. 79 99:59:59,999 --> 99:59:59,999 The result is basically a word processor of genes. 80 99:59:59,999 --> 99:59:59,999 You can take an entire gene out, put one in, 81 99:59:59,999 --> 99:59:59,999 or even edit just a single letter within a gene. 82 99:59:59,999 --> 99:59:59,999 And you can do it in nearly any species. 83 99:59:59,999 --> 99:59:59,999 Okay, remember how I said that gene drives 84 99:59:59,999 --> 99:59:59,999 originally had two problems? 85 99:59:59,999 --> 99:59:59,999 The first is that it was hard to engineer a mosquito 86 99:59:59,999 --> 99:59:59,999 to be malaria resistant. 87 99:59:59,999 --> 99:59:59,999 That's basically gone now, thanks to CRISPR. 88 99:59:59,999 --> 99:59:59,999 But the other problem was logistical. 89 99:59:59,999 --> 99:59:59,999 How do you get your trait to spread? 90 99:59:59,999 --> 99:59:59,999 This is where it gets clever. 91 99:59:59,999 --> 99:59:59,999 A couple years ago, a biologist at Harvard named Kevin Esvelt 92 99:59:59,999 --> 99:59:59,999 wondered what would happen if you made it so that 93 99:59:59,999 --> 99:59:59,999 CRISPR inserted not only your new gene, 94 99:59:59,999 --> 99:59:59,999 but also the machinery that does the cutting and pasting. 95 99:59:59,999 --> 99:59:59,999 In other words, what if CRISPR also copy and pasted itself. 96 99:59:59,999 --> 99:59:59,999 You'd end up with a perpetual motion machine for gene editing. 97 99:59:59,999 --> 99:59:59,999 And that's exactly what happened. 98 99:59:59,999 --> 99:59:59,999 This CRISPR gene drive that Esvelt created 99 99:59:59,999 --> 99:59:59,999 not only guarantees that a trait will get passed on, 100 99:59:59,999 --> 99:59:59,999 but if its used in the germline cell, 101 99:59:59,999 --> 99:59:59,999 it will automatically copy and paste your new gene 102 99:59:59,999 --> 99:59:59,999 into both chromosomes of every single individual. 103 99:59:59,999 --> 99:59:59,999 It's like a global search and replace, 104 99:59:59,999 --> 99:59:59,999 or in science terms, 105 99:59:59,999 --> 99:59:59,999 it makes a heterozygous trait homozygous. 106 99:59:59,999 --> 99:59:59,999 So, what does this mean? 107 99:59:59,999 --> 99:59:59,999 For one thing, it means we have a very powerful, 108 99:59:59,999 --> 99:59:59,999 but also somewhat alarming new tool. 109 99:59:59,999 --> 99:59:59,999 Up until now, the fact that gene drives didn't work very well 110 99:59:59,999 --> 99:59:59,999 was actually kind of a relief. 111 99:59:59,999 --> 99:59:59,999 Normally when we mess around with an organisms's genes, 112 99:59:59,999 --> 99:59:59,999 we make that thing less evolutionarily fit. 113 99:59:59,999 --> 99:59:59,999 So biologists can make all the mutant fruit flies they want 114 99:59:59,999 --> 99:59:59,999 without worrying about it. 115 99:59:59,999 --> 99:59:59,999 If some escape, natural selection just takes care of it. 116 99:59:59,999 --> 99:59:59,999 What's remarkable and powerful and frightening about gene drives 117 99:59:59,999 --> 99:59:59,999 is that that will no longer be true. 118 99:59:59,999 --> 99:59:59,999 Assuming that your trait does not have a big evolutionary handicap, 119 99:59:59,999 --> 99:59:59,999 like a mosquito that can't fly, 120 99:59:59,999 --> 99:59:59,999 the CRISPR-based gene drive will spread the change relentlessly 121 99:59:59,999 --> 99:59:59,999 until it is in every single individual in the population.