9:59:59.000,9:59:59.000 So this is a talk about gene drives, 9:59:59.000,9:59:59.000 but I'm going to start by [br]telling you a brief story. 9:59:59.000,9:59:59.000 20 years ago, a biologist[br]named Anthony James 9:59:59.000,9:59:59.000 got obsessed by the idea[br]of making mosquitos 9:59:59.000,9:59:59.000 that didn't transmit malaria. 9:59:59.000,9:59:59.000 It was a great idea,[br]but pretty much a complete failure. 9:59:59.000,9:59:59.000 For one thing, it turned out to be[br]really hard 9:59:59.000,9:59:59.000 to make a malaria resistant mosquito. 9:59:59.000,9:59:59.000 James managed it, finally,[br]just a few years ago 9:59:59.000,9:59:59.000 by adding some genes[br]that make it impossible[br] 9:59:59.000,9:59:59.000 for the malaria gene[br]to survive inside the mosquito. 9:59:59.000,9:59:59.000 But that just created another problem. 9:59:59.000,9:59:59.000 Now that you've got malaria-resistant[br]mosquito, 9:59:59.000,9:59:59.000 how do you get it to replace[br]all the malaria-carrying mosquitos? 9:59:59.000,9:59:59.000 There are a couple options, 9:59:59.000,9:59:59.000 but plan A was basically to breed up[br]a bunch of the new genetically-engineered mosquotos, 9:59:59.000,9:59:59.000 release them into the wild, 9:59:59.000,9:59:59.000 and hope that they pass on their genes. 9:59:59.000,9:59:59.000 The problem was that you'd [br]have to release 9:59:59.000,9:59:59.000 literally 10x the number of native[br]mosquitos to work. 9:59:59.000,9:59:59.000 So in a village with 10,000 mosquitos, 9:59:59.000,9:59:59.000 you release an extra 100,000. 9:59:59.000,9:59:59.000 As you might guess, this was not[br]a very popular strategy 9:59:59.000,9:59:59.000 with the villagers. 9:59:59.000,9:59:59.000 (Laughter) 9:59:59.000,9:59:59.000 Then, last January, Anthony James[br]got an email[br] 9:59:59.000,9:59:59.000 from a biologist named [br]Ethan Bier. 9:59:59.000,9:59:59.000 Bier said that he and his grad student,[br]Valentino Gantz,[br] 9:59:59.000,9:59:59.000 had stumbled on a tool that could not only[br]guarentee 9:59:59.000,9:59:59.000 that a particular gene trait[br]would not be inherited, 9:59:59.000,9:59:59.000 but that it would spread[br]incredibly quickly. 9:59:59.000,9:59:59.000 If they were right, it would basically[br]solve the problem[br] 9:59:59.000,9:59:59.000 that he and James had been[br]working on for 20 years. 9:59:59.000,9:59:59.000 As a test, they engineered[br]two mosquitos 9:59:59.000,9:59:59.000 to carry the anti-malaria gene 9:59:59.000,9:59:59.000 and also this new tool,[br]a gene drive, 9:59:59.000,9:59:59.000 which I'll explain in a minute. 9:59:59.000,9:59:59.000 Finally, they set it up so that[br]any mosquitos 9:59:59.000,9:59:59.000 that had inherited the[br]anti-malaria gene 9:59:59.000,9:59:59.000 wouldn't have the usual white eyes,[br]but would instead have red eyes. 9:59:59.000,9:59:59.000 That was pretty much just [br]for convenience 9:59:59.000,9:59:59.000 so they could tell just at a glance[br]which was which. 9:59:59.000,9:59:59.000 So they took their two [br]anti-malarial, red eye mosquitos 9:59:59.000,9:59:59.000 and put them in a box with 30[br]ordinary white-eyed ones 9:59:59.000,9:59:59.000 and let them breed. 9:59:59.000,9:59:59.000 In two generations, [br]those had produced 38,000 grandchildren. 9:59:59.000,9:59:59.000 That is not the surprising part. 9:59:59.000,9:59:59.000 This is the surprising part: 9:59:59.000,9:59:59.000 given that you started with just[br]two red-eyed mosquitos 9:59:59.000,9:59:59.000 and 30 white-eyed ones, 9:59:59.000,9:59:59.000 you expect mostly white-eyed[br]descendents. 9:59:59.000,9:59:59.000 Instead, when James opened the box, 9:59:59.000,9:59:59.000 all 38,000 mosquitos had red eyes. 9:59:59.000,9:59:59.000 When I asked Ethan Bier[br]about this moment, 9:59:59.000,9:59:59.000 he became so excited, tht he was[br]literally shouting into the phone. 9:59:59.000,9:59:59.000 That's because getting only[br]red-eyed mosquitos 9:59:59.000,9:59:59.000 violates a rule that is the[br]absolute cornerstone of biology, 9:59:59.000,9:59:59.000 Mendelian genetics. 9:59:59.000,9:59:59.000 I'll keep this quick, but Mendelian genetics[br]says when a male and female mate, 9:59:59.000,9:59:59.000 their baby inherits half of its[br]DNA from each parent. 9:59:59.000,9:59:59.000 So if our original mosquito was aa[br]and our new mosquito is aB, 9:59:59.000,9:59:59.000 where B is the anti-malarial gene, 9:59:59.000,9:59:59.000 the babies should come out[br]in four permutations: 9:59:59.000,9:59:59.000 aa, aB, aa and Ba. 9:59:59.000,9:59:59.000 Instead, with the new gene drive, 9:59:59.000,9:59:59.000 they all came out aB. 9:59:59.000,9:59:59.000 Biologically, that shouldn't[br]even be possible. 9:59:59.000,9:59:59.000 So what happened? 9:59:59.000,9:59:59.000 The first thing that happened[br]was the arrival 9:59:59.000,9:59:59.000 of a gene-editing tool[br]known as CRISPR in 2012. 9:59:59.000,9:59:59.000 Many of you have probably heard[br]about CRISPR, 9:59:59.000,9:59:59.000 so I'll just say briefly that CRISPR[br]is a tool that allows researchers 9:59:59.000,9:59:59.000 to edit genes very precisely,[br]easily and quickly. 9:59:59.000,9:59:59.000 It does this by harnessing a mechanism[br]that already existed in bacteria. 9:59:59.000,9:59:59.000 Basically, there's a protein[br]that acts like a scissors 9:59:59.000,9:59:59.000 and cuts the DNA, 9:59:59.000,9:59:59.000 and there's an RNA molecule[br]that directs the scissors 9:59:59.000,9:59:59.000 to any point on the genome you want. 9:59:59.000,9:59:59.000 The result is basically a word processor[br]of genes. 9:59:59.000,9:59:59.000 You can take an entire gene out,[br]put one in, 9:59:59.000,9:59:59.000 or even edit just a single letter[br]within a gene. 9:59:59.000,9:59:59.000 And you can do it in nearly any species. 9:59:59.000,9:59:59.000 Okay, remember how I said [br]that gene drives 9:59:59.000,9:59:59.000 originally had two problems? 9:59:59.000,9:59:59.000 The first is that it was hard[br]to engineer a mosquito 9:59:59.000,9:59:59.000 to be malaria resistant. 9:59:59.000,9:59:59.000 That's basically gone now,[br]thanks to CRISPR. 9:59:59.000,9:59:59.000 But the other problem was [br]logistical. 9:59:59.000,9:59:59.000 How do you get your trait to spread? 9:59:59.000,9:59:59.000 This is where it gets clever. 9:59:59.000,9:59:59.000 A couple years ago, a biologist[br]at Harvard named Kevin Esvelt 9:59:59.000,9:59:59.000 wondered what would happen[br]if you made it so that 9:59:59.000,9:59:59.000 CRISPR inserted not only[br]your new gene, 9:59:59.000,9:59:59.000 but also the machinery [br]that does the cutting and pasting. 9:59:59.000,9:59:59.000 In other words, what if CRISPR[br]also copy and pasted itself. 9:59:59.000,9:59:59.000 You'd end up with a perpetual[br]motion machine for gene editing. 9:59:59.000,9:59:59.000 And that's exactly what happened. 9:59:59.000,9:59:59.000 This CRISPR gene drive[br]that Esvelt created 9:59:59.000,9:59:59.000 not only guarantees that a trait [br]will get passed on, 9:59:59.000,9:59:59.000 but if its used in the germline cell, 9:59:59.000,9:59:59.000 it will automatically copy and paste[br]your new gene 9:59:59.000,9:59:59.000 into both chromosomes of every[br]single individual. 9:59:59.000,9:59:59.000 It's like a global search and replace, 9:59:59.000,9:59:59.000 or in science terms, 9:59:59.000,9:59:59.000 it makes a heterozygous trait[br]homozygous. 9:59:59.000,9:59:59.000 So, what does this mean? 9:59:59.000,9:59:59.000 For one thing, it means we have[br]a very powerful, 9:59:59.000,9:59:59.000 but also somewhat alarming new tool. 9:59:59.000,9:59:59.000 Up until now, the fact that gene drives[br]didn't work very well 9:59:59.000,9:59:59.000 was actually kind of a relief. 9:59:59.000,9:59:59.000 Normally when we mess around[br]with an organisms's genes, 9:59:59.000,9:59:59.000 we make that thing less evolutionarily fit. 9:59:59.000,9:59:59.000 So biologists can make all the mutant[br]fruit flies they want 9:59:59.000,9:59:59.000 without worrying about it. 9:59:59.000,9:59:59.000 If some escape, natural selection[br]just takes care of it. 9:59:59.000,9:59:59.000 What's remarkable and powerful[br]and frightening about gene drives 9:59:59.000,9:59:59.000 is that that will no longer be true. 9:59:59.000,9:59:59.000 Assuming that your trait does not[br]have a big evolutionary handicap, 9:59:59.000,9:59:59.000 like a mosquito that can't fly, 9:59:59.000,9:59:59.000 the CRISPR-based gene drive[br]will spread the change relentlessly 9:59:59.000,9:59:59.000 until it is in every single individual[br]in the population. 9:59:59.000,9:59:59.000 Now, it isn't easy to make[br]a gene drive that works that well, 9:59:59.000,9:59:59.000 but James and Esvelt think[br]that we can. 9:59:59.000,9:59:59.000 The good news is that this opens[br]the door to some remarkable things. 9:59:59.000,9:59:59.000 If you put an anti-malarial gene drive[br]in just 1 percent 9:59:59.000,9:59:59.000 of anopheles mosquitos,[br]the species that transmits malaria. 9:59:59.000,9:59:59.000 Researchers estimate that it would[br]spread to the entire population 9:59:59.000,9:59:59.000 in a year. 9:59:59.000,9:59:59.000 So in a year, you could virtually [br]eliminate malaria. 9:59:59.000,9:59:59.000 In practice, we're still a few years out[br]from being able to do that, 9:59:59.000,9:59:59.000 but sitll, a 1,000 children a day[br]die of malaria. 9:59:59.000,9:59:59.000 In a year, that number could be[br]almost zero. 9:59:59.000,9:59:59.000 The same goes for dengue fever,[br]chicken genuang (?), yellow fever. 9:59:59.000,9:59:59.000 And it gets better. 9:59:59.000,9:59:59.000 Say you want to get rid [br]of an invasive species, 9:59:59.000,9:59:59.000 like get Asian Carp out of[br]The Great Lakes. 9:59:59.000,9:59:59.000 All you have to do is release [br]a gene drive 9:59:59.000,9:59:59.000 that makes the fish produce[br]only male offspring. 9:59:59.000,9:59:59.000 In a few generations, there'll be[br]no females left, no more carp. 9:59:59.000,9:59:59.000 In theory, this means that we [br]could restore hundreds 9:59:59.000,9:59:59.000 of native species that have been[br]pushed to the brink. 9:59:59.000,9:59:59.000 Okay, that's the good news, 9:59:59.000,9:59:59.000 this is the bad news. 9:59:59.000,9:59:59.000 Gene drives are so effective, 9:59:59.000,9:59:59.000 that even an accidental release [br]could change an entire species, 9:59:59.000,9:59:59.000 and often very quickly. 9:59:59.000,9:59:59.000 Anthony James took the precautions. 9:59:59.000,9:59:59.000 He breed his mosquitos in[br]a bio-containment lab 9:59:59.000,9:59:59.000 and he also used a species[br]that's not native to the US 9:59:59.000,9:59:59.000 so that even if some did escape, 9:59:59.000,9:59:59.000 they'd just die off, 9:59:59.000,9:59:59.000 there'd be nothing for them[br]to mate with. 9:59:59.000,9:59:59.000 But it's also true that if [br]a dozen Asian Carp 9:59:59.000,9:59:59.000 with the all-male gene drive accidentally[br]got carried from The Great Lakes 9:59:59.000,9:59:59.000 back to Asia, 9:59:59.000,9:59:59.000 they could potentially wipe out [br]the native Asian Carp population. 9:59:59.000,9:59:59.000 And that's not so unlikely, given[br]how connected our world is. 9:59:59.000,9:59:59.000 In fact, it's why we have [br]an invasive species problem. 9:59:59.000,9:59:59.000 And that's fish. 9:59:59.000,9:59:59.000 Things like mosquitos and fruit flies,[br]there's literally no way to contain them. 9:59:59.000,9:59:59.000 They cross borders and oceans[br]all the time. 9:59:59.000,9:59:59.000 Okay, the other piece of bad news[br]is that 9:59:59.000,9:59:59.000 a gene drive might not stay confined[br]to what we call the target species. 9:59:59.000,9:59:59.000 That's because of gene flow, 9:59:59.000,9:59:59.000 which is a fancy way of saying[br]that neighboring species 9:59:59.000,9:59:59.000 sometimes inter-breed. 9:59:59.000,9:59:59.000 If that happens, it's possible[br]a gene drive could cross over, 9:59:59.000,9:59:59.000 like Asian Carp could infect[br]some other kind of Carp. 9:59:59.000,9:59:59.000 That's not so bad if your drive[br]just promotes a trait, like eye color. 9:59:59.000,9:59:59.000 In fact, there's a decent chance that[br]we'll see a wave 9:59:59.000,9:59:59.000 of very weird fruit flies [br]in the near future. 9:59:59.000,9:59:59.000 But it could be a disaster[br]if your drive is deigned 9:59:59.000,9:59:59.000 to eliminate the species entirely. 9:59:59.000,9:59:59.000 The last worrisome thing is that[br]the technology to do this, 9:59:59.000,9:59:59.000 to genetically engineer an organism[br]and include a gene drive 9:59:59.000,9:59:59.000 is something basically any lab[br]in the world can do. 9:59:59.000,9:59:59.000 An undergraduate can do it. 9:59:59.000,9:59:59.000 A talented high schooler[br]with some equipment can do it. 9:59:59.000,9:59:59.000 Now I'm guessing that this sounds [br]terrifying. 9:59:59.000,9:59:59.000 Interestingly though, nearly [br]every scientist I talk to 9:59:59.000,9:59:59.000 seems to think that gene drives[br]were not actually 9:59:59.000,9:59:59.000 that frightening or dangerous. 9:59:59.000,9:59:59.000 Partly because they believe that[br]scientists will be 9:59:59.000,9:59:59.000 very cautious and responsible[br]about using them. 9:59:59.000,9:59:59.000 (Laughter) 9:59:59.000,9:59:59.000 So far, that's been true. 9:59:59.000,9:59:59.000 The gene drives also have[br]some actual limitations. 9:59:59.000,9:59:59.000 For one thing, they work in only[br]sexually reproducing species. 9:59:59.000,9:59:59.000 So thank goodness, they can't be used[br]to engineer viruses or bacteria. 9:59:59.000,9:59:59.000 Also, the trait spreads only with each[br]succesive genertion. 9:59:59.000,9:59:59.000 So changing or eliminating a population[br]is practical only if that species 9:59:59.000,9:59:59.000 has a fast reproductive cycle,[br] 9:59:59.000,9:59:59.000 like insects or maybe small vertebrates[br]like mice or fish. 9:59:59.000,9:59:59.000 In elephants or people, it would[br]take centuries 9:59:59.000,9:59:59.000 for a trait to spread widely enough[br]to matter. 9:59:59.000,9:59:59.000 Also, even with CRISPR, it's not that easy[br]to engineer a truly devastating trait. 9:59:59.000,9:59:59.000 Say you wanted to make a fruit fly[br] 9:59:59.000,9:59:59.000 that feeds on ordinary fruit instead[br]of rotten fruit 9:59:59.000,9:59:59.000 with the aim of sabotaging [br]American agriculture. 9:59:59.000,9:59:59.000 First you'd have to figure out[br]which gene controls 9:59:59.000,9:59:59.000 what the fly wants to eat, 9:59:59.000,9:59:59.000 which is already a very long [br]and complicated project. 9:59:59.000,9:59:59.000 Then you'd have to alter those genes[br]to change the fly's behavior 9:59:59.000,9:59:59.000 to whatever you'd want it to be, 9:59:59.000,9:59:59.000 which is an even longer [br]and complicated project. 9:59:59.000,9:59:59.000 And it might not even work because[br]the genes that control behavior are complex. 9:59:59.000,9:59:59.000 So if you're a terrorist and have [br]to choose between 9:59:59.000,9:59:59.000 starting a grueling basic research program 9:59:59.000,9:59:59.000 that will require years [br]of meticulous lab work 9:59:59.000,9:59:59.000 and still might not pan out, 9:59:59.000,9:59:59.000 or just blowing stuff up? 9:59:59.000,9:59:59.000 You'll probably choose the later. 9:59:59.000,9:59:59.000 This is especially true because[br]at least in theory, 9:59:59.000,9:59:59.000 it should be pretty easy to build[br]what's called a reversal drive. 9:59:59.000,9:59:59.000 That's one that basically overwrites[br]the change made by the first gene drive. 9:59:59.000,9:59:59.000 So if you don't like the effects [br]of a change, 9:59:59.000,9:59:59.000 you can just release a second drive[br]that will cancel it out, 9:59:59.000,9:59:59.000 at least in theory. 9:59:59.000,9:59:59.000 Okay, so where does this leave us? 9:59:59.000,9:59:59.000 We now have the ability to change[br]entire species at will. 9:59:59.000,9:59:59.000 Should we? 9:59:59.000,9:59:59.000 Are we gods now? 9:59:59.000,9:59:59.000 I'm not sure I'd say that. 9:59:59.000,9:59:59.000 But I would say this: 9:59:59.000,9:59:59.000 First, some very smart people[br]are even now debating 9:59:59.000,9:59:59.000 how to regulate gene drives. 9:59:59.000,9:59:59.000 At the same time, some other[br]very smart people 9:59:59.000,9:59:59.000 are working hard to create[br]safeguards, 9:59:59.000,9:59:59.000 like gene drives that self regulate[br]or petter out after a few generations. 9:59:59.000,9:59:59.000 But this technology still requires[br]a conversation. 9:59:59.000,9:59:59.000 And given the nature of gene drives, 9:59:59.000,9:59:59.000 that conversation has to be global. 9:59:59.000,9:59:59.000 What if Kenya wants to use a drive[br]that Tanzania doesn't? 9:59:59.000,9:59:59.000 Who decides whether to release[br]a gene drive that can fly? 9:59:59.000,9:59:59.000 I don't have the answer to that question. 9:59:59.000,9:59:59.000 All we can do going forward, I think, 9:59:59.000,9:59:59.000 is talk honestly about [br]the risks and benefits 9:59:59.000,9:59:59.000 and take responsibility for our choices. 9:59:59.000,9:59:59.000 By that I mean, not just the choice[br]to use a gene drive, 9:59:59.000,9:59:59.000 but also the choice not to use one