WEBVTT - Reshaping Nature Through Gene Drives 0:00:15.250 --> 0:00:28.890 Pushkin, you're listening to Brave New Planet, a podcast about 0:00:28.930 --> 0:00:33.090 amazing new technologies that could dramatically improve our world, or 0:00:33.490 --> 0:00:36.050 if we don't make wise choices, could leave us a 0:00:36.050 --> 0:00:40.730 lot worse off. Utopia or dystopia. It's up to us. 0:00:47.970 --> 0:00:52.450 On October eighth, seventeen sixty nine, James Cook, an explorer 0:00:52.570 --> 0:00:55.770 and captain in the British Royal Navy, became the first 0:00:55.810 --> 0:00:58.690 European to set foot on the islands that are today 0:00:58.770 --> 0:01:03.970 known as New Zealand. His arrival would have dramatic consequences 0:01:04.010 --> 0:01:07.130 for the Maori people that had inhabited the land for 0:01:07.330 --> 0:01:12.530 hundreds of years. It would also radically alter New Zealand's ecology, 0:01:13.250 --> 0:01:16.930 because when Cook disembarked, so too did some of the 0:01:17.010 --> 0:01:21.570 rats that did hitchhike on his ship. Previously unknown to 0:01:21.690 --> 0:01:25.410 the Pacific Islands, these rodents grew in population over the 0:01:25.490 --> 0:01:29.930 centuries and wreaked havoc on the environment. We're in the 0:01:29.970 --> 0:01:34.210 middle of a rodent nami. You've seen the headlines. Rats 0:01:34.330 --> 0:01:38.610 as big as cats. Rats everywhere. It is a problem too, 0:01:38.690 --> 0:01:43.650 everywhere that you wouldn't believes. Hey, we've probably got the 0:01:43.690 --> 0:01:46.490 most rats that double the most rats with ever head 0:01:46.810 --> 0:01:51.370 shocking actually jsay shocking, and it's not just unpleasantness that's 0:01:51.410 --> 0:01:56.090 the problem. The rats and other invasive mammals have been 0:01:56.290 --> 0:02:00.930 decimating New Zealand's birds. They devoured tens of millions of 0:02:00.970 --> 0:02:05.130 eggs and baby birds every year, causing the extinction of 0:02:05.370 --> 0:02:10.210 one quarter of the nation's unique bird species. New Zealand 0:02:10.210 --> 0:02:13.330 has long tried to get rid of these invaders. The 0:02:13.450 --> 0:02:16.890 traditional answer has been to spread rat poison all over 0:02:16.930 --> 0:02:22.410 the islands, often by helicopters, but rat poison is indiscriminate. 0:02:22.970 --> 0:02:27.410 Native animals can also die from eating it. Sometimes humans 0:02:27.490 --> 0:02:34.810 accidentally consume it as well, and it hasn't solved the problem. Recently, 0:02:35.050 --> 0:02:39.490 scientists have proposed a much more targeted solution. It's called 0:02:39.690 --> 0:02:44.330 a gene drive, a genetic engineering trick that guarantees that 0:02:44.450 --> 0:02:48.890 when two animals mate, a specific gene will be inherited 0:02:49.330 --> 0:02:54.810 by one hundred percent of their progeny. In time, any gene, 0:02:55.290 --> 0:03:01.170 even a disadvantageous gene, would spread through the population. If 0:03:01.210 --> 0:03:04.810 New Zealand were to release genetically engineered rats with a 0:03:04.930 --> 0:03:09.490 gene drive, to dramatically decrease the rat's fertility, while the 0:03:09.650 --> 0:03:16.130 rat population would shrink, In effect, evolution could be directed 0:03:16.410 --> 0:03:20.330 to vote the rats off the islands. And it's not 0:03:20.410 --> 0:03:24.490 just rats. Gene drives might be used against any invasive 0:03:24.570 --> 0:03:29.050 animal or plant that uses sexual reproduction, and they might 0:03:29.130 --> 0:03:33.090 also be used to save species, for example, by helping 0:03:33.090 --> 0:03:38.490 them survive the effects of climate change. Most importantly, gene 0:03:38.530 --> 0:03:43.810 drives might save millions of lives by eliminating or modifying 0:03:43.810 --> 0:03:48.890 the mosquito that's primarily responsible for spreading malaria throughout sub 0:03:48.930 --> 0:03:53.410 Saharan Africa. Now, no one has yet deployed gene drives 0:03:53.450 --> 0:03:55.930 in the wild, but they've been shown to work in 0:03:55.970 --> 0:04:03.450 the laboratory reshaping nature. It's a heady concept. Scientists are 0:04:03.610 --> 0:04:08.130 exhilarated by the possibilities for improving the world. At the 0:04:08.170 --> 0:04:16.330 same time they're wondering what could possibly go wrong. Today's 0:04:16.370 --> 0:04:19.930 big question. Should we use gene drives to correct the 0:04:19.970 --> 0:04:24.770 past introduction of invasive species, protect species from the ravages 0:04:24.810 --> 0:04:29.330 of climate change, and save humans from serious infectious diseases 0:04:30.170 --> 0:04:34.770 or is it too risky? Evolution in ecology, after all, 0:04:35.010 --> 0:04:39.730 can be strangely unpredictable. When might the risks be justified? 0:04:40.330 --> 0:04:44.970 And when you're proposing to release things into nature, who 0:04:45.490 --> 0:04:54.450 needs to say yes. My name is Eric Lander. I'm 0:04:54.490 --> 0:04:57.290 a scientist who works on ways to improve human health. 0:04:57.650 --> 0:05:00.370 I helped lead the Human Genome Project, and today I 0:05:00.490 --> 0:05:03.890 lead the Road Institute of MIT and Harvard. In the 0:05:03.930 --> 0:05:07.730 twenty first century, powerful technologies have been appearing at a 0:05:07.810 --> 0:05:13.010 breathtaking pace, related to the Internet, artificial intelligence, genetic engineering, 0:05:13.010 --> 0:05:17.650 and more. They have amazing potential upsides, but we can't 0:05:17.650 --> 0:05:21.090 ignore the risks that come with them. The decisions aren't 0:05:21.090 --> 0:05:24.850 just up to scientists or politicians, whether we like it 0:05:24.970 --> 0:05:28.170 or not, we all of us are the stewards of 0:05:28.170 --> 0:05:31.930 a brave New planet. This generation's choices will shape the 0:05:31.970 --> 0:05:40.650 future as never before. Coming up on this episode of 0:05:40.730 --> 0:05:46.330 Brave New Planets, we speak to scientists who played a 0:05:46.410 --> 0:05:50.530 key role in inventing gene drives. This is potentially a 0:05:50.730 --> 0:05:56.690 much more elegant way of solving ecological problems than poisons 0:05:56.690 --> 0:05:59.650 and bulldozers. We talk with people trying to balance the 0:05:59.730 --> 0:06:03.210 benefits and risks. Okay, so people are looking at using 0:06:03.210 --> 0:06:07.810 genetic engineering to alter wild species. This is really exciting 0:06:08.090 --> 0:06:10.770 and at the same time I'm literally in the same breath, 0:06:10.890 --> 0:06:15.490 I was also just like, holy crap, if this isn't 0:06:15.570 --> 0:06:19.130 used properly, this could be really damaging to our planet. 0:06:19.930 --> 0:06:23.290 We hear from a scientist in Burkina Fasso who wants 0:06:23.330 --> 0:06:26.650 to use gene drives to get rid of malaria. This 0:06:26.730 --> 0:06:29.410 is really my dream and my hope that I can 0:06:29.490 --> 0:06:31.610 come up with something that kind of really helps not 0:06:31.650 --> 0:06:37.610 only Africa. And a journalist from Kenya who's pretty skeptical. 0:06:38.290 --> 0:06:41.450 It's very nice to think that people really care about 0:06:41.490 --> 0:06:43.570 the lives of Africans, But I think the story is 0:06:43.610 --> 0:06:53.330 a lot more complex than that. Stay tuned. Chapter one 0:06:53.890 --> 0:07:00.530 snails the size of baseballs. To understand the reasons why 0:07:00.530 --> 0:07:03.490 people might want to use gene drives, I talked with 0:07:03.570 --> 0:07:07.090 someone who's thought a lot about them. My name is 0:07:07.450 --> 0:07:11.010 doctor James Collins go by Jim, a professor in the 0:07:11.050 --> 0:07:14.730 School of Life Sciences at Arizona State University. Jim is 0:07:14.770 --> 0:07:17.810 an evolutionary ecollegist who co chaired a study on gene 0:07:17.890 --> 0:07:21.650 drives for the US National Academy of Sciences. For an 0:07:21.650 --> 0:07:25.130 evolutionary ecologist, he has a bit of an unusual upbringing. 0:07:25.810 --> 0:07:29.770 I grew up in New York City, Queens and always 0:07:29.810 --> 0:07:33.290 just had a love of plants and animals. In New 0:07:33.370 --> 0:07:36.490 York City. In New York City, Queens at the time 0:07:36.690 --> 0:07:40.730 was different than Queens today. I could go fishing. I 0:07:40.770 --> 0:07:46.210 could catch turtles and snakes and frogs, all kinds of insects, 0:07:46.610 --> 0:07:51.370 bring them home to my very tolerant parents. Jim knows 0:07:51.410 --> 0:07:54.490 a lot about how ecosystems can be disrupted by the 0:07:54.490 --> 0:07:59.410 introduction of new species, from microbes to mammals. He told 0:07:59.450 --> 0:08:02.730 me that Captain Cook was responsible for more than just 0:08:02.810 --> 0:08:09.090 introducing rats into New Zealand. Think about Hawaiian birds where 0:08:08.850 --> 0:08:13.850 they are endangered by avian malaria, and that's as a 0:08:13.930 --> 0:08:20.210 result of a mosquito being introduced by Captain Cook. Then 0:08:20.530 --> 0:08:24.770 the colonists brought chickens, and they brought avian malaria. The 0:08:24.850 --> 0:08:30.810 mosquitoes begin to feed on the chickens, acquire the malaria, 0:08:30.890 --> 0:08:34.010 and then begin to feed on native birds, transmit the 0:08:34.050 --> 0:08:38.570 malaria to native birds, and they are being diminished in 0:08:38.650 --> 0:08:42.450 terms of population sizes, and even species. In fact, Hawaii 0:08:42.770 --> 0:08:46.730 has become the bird extinction capital of the world. Since 0:08:46.810 --> 0:08:50.530 humans arrived ninety five, one hundred and forty two birds 0:08:50.570 --> 0:08:55.050 species found nowhere else in the world have become extinct 0:08:55.330 --> 0:08:59.530 in Hawaii. Even small scale introduction of a new species 0:08:59.850 --> 0:09:04.690 can lead to massive problems. In nineteen sixty six, a 0:09:04.770 --> 0:09:08.250 young boy who was vacationing in Hawaii decided to take 0:09:08.250 --> 0:09:11.370 a few of the giant land snails that live there 0:09:11.850 --> 0:09:14.650 back to his home in Miami to keep them as 0:09:14.690 --> 0:09:19.010 pets in the family garden. The snails, which can grow 0:09:19.170 --> 0:09:23.970 larger than the size of baseballs, reproduced quickly. They soon 0:09:24.010 --> 0:09:27.370 began to cause economic damage to local farms, and they 0:09:27.410 --> 0:09:32.170 also carried dangerous parasites slithering along at quite literally a 0:09:32.330 --> 0:09:35.730 snail's pace. They certainly don't look menacing, but for the 0:09:35.730 --> 0:09:39.970 Florida Department of Agriculture, this is a horror movie. The 0:09:40.090 --> 0:09:43.250 problem with these things They love just about anything that 0:09:43.290 --> 0:09:48.410 grows in Florida. The eradication effort, which used poisons, took 0:09:48.530 --> 0:09:52.890 ten years and cost over a million dollars, but despite 0:09:52.930 --> 0:09:57.570 all the work, the snail population eventually bounced back. In 0:09:57.650 --> 0:10:01.730 twenty fourteen, the Florida Department of Agriculture went door to 0:10:01.930 --> 0:10:06.250 door searching for the snails. They found a hundred and 0:10:06.410 --> 0:10:11.810 fifty thousands, with two properties alone harboring seven hundred of 0:10:11.810 --> 0:10:15.850 the critters. With other invasive species, the measures have been 0:10:15.930 --> 0:10:20.410 even more dramatic. In the nineteen fifties, Australia tried to 0:10:20.450 --> 0:10:25.050 exterminate an escalating population of European rabbits that had been 0:10:25.090 --> 0:10:30.330 introduced a century earlier by an English settler. Their solution 0:10:30.490 --> 0:10:34.930 was to release rabbits carrying a deadly Mixoma virus. It 0:10:35.170 --> 0:10:39.530 killed millions of rabbits across Australia, but it didn't solve 0:10:39.570 --> 0:10:44.130 the problem. There are hundreds of invasive species that people 0:10:44.170 --> 0:10:46.810 would like to be rid of, zebra muscles in the 0:10:46.810 --> 0:10:50.970 Great Lakes, silver carp in the Missouri River, kudzuweed, and 0:10:51.090 --> 0:10:56.250 Georgia burmese pythons in the Everglades. But the species that 0:10:56.450 --> 0:11:01.170 cause the most harm to humans aren't recent invaders. They're 0:11:01.170 --> 0:11:06.810 indigenous mosquitoes that spread malaria in Africa. My name is 0:11:06.850 --> 0:11:09.930 Diane Worth. I'm on the faculty at the Harvard chan 0:11:10.050 --> 0:11:13.650 School of Public Health. I work on malaria. Diane is 0:11:13.690 --> 0:11:16.450 also a colleague of mine at the Broad Institute, and 0:11:16.570 --> 0:11:22.130 she studied malaria for over thirty five years. Malaria starts 0:11:22.170 --> 0:11:26.410 as a fever and chills. It has nondescript symptoms in 0:11:26.450 --> 0:11:31.330 the early stages, but then as the disease progresses, people 0:11:31.370 --> 0:11:34.690 can go into a coma, they get very sick, and 0:11:34.810 --> 0:11:40.770 it spreads by mosquitoes. That's right. The disease is transmitted 0:11:41.090 --> 0:11:47.730 by the anopling mosquito in Africa. That's Avelis Gambia, a 0:11:47.770 --> 0:11:52.250 mosquito that's very efficient at transmitting malaria. The world has 0:11:52.410 --> 0:11:55.330 tried to eradicate malaria once before, in the middle of 0:11:55.330 --> 0:12:00.290 the last century, when they had DDT and chloroquin DDT 0:12:00.490 --> 0:12:04.970 to kill mosquitos and chloroquin to treat infected people, and 0:12:05.170 --> 0:12:09.490 that effort did lead to some successes. Malaria was eated 0:12:09.610 --> 0:12:13.450 from Italy, from most of Southern Europe, from the United 0:12:13.490 --> 0:12:21.490 States by a combination of those techniques and environmental activities, 0:12:21.530 --> 0:12:24.890 including putting oil on the top of water so it 0:12:24.930 --> 0:12:28.050 wouldn't be environmentally allowed now, but was done in the 0:12:28.090 --> 0:12:31.690 Tennessee Valley here in the United States in the nineteen fifties. 0:12:32.330 --> 0:12:36.450 And that effort failed in most of the world, and 0:12:36.530 --> 0:12:40.650 in fact, that effort really never included Sub Saharan Africa, 0:12:40.730 --> 0:12:44.770 because the experts at the time concluded that in Sub 0:12:44.810 --> 0:12:49.650 Saharan Africa, transmission was so intense that no effort could 0:12:49.730 --> 0:12:52.650 bring it under control. How are we doing in the 0:12:52.690 --> 0:12:56.130 elimination of malaria today. I think what's happened in the 0:12:56.170 --> 0:13:00.290 last decade is two things. One, there's been an overall 0:13:00.370 --> 0:13:05.530 reduction in the number of cases of malaria through increased 0:13:05.930 --> 0:13:12.170 distribution of bednets, better diagnostics, better use of treatment drugs. 0:13:12.610 --> 0:13:17.530 We've dropped cases by forty percent worldwide and deaths by 0:13:17.570 --> 0:13:21.530 about fifty percent worldwide. The other part of the story 0:13:21.890 --> 0:13:27.770 is really sub Saharan Africa, where progress has slowed and 0:13:27.890 --> 0:13:34.090 in many cases reversed. For example, Nigeria has twenty five 0:13:34.290 --> 0:13:37.810 percent of all of the malaria in the world, and 0:13:38.130 --> 0:13:42.850 ten countries make up seventy percent of the burden of 0:13:42.890 --> 0:13:47.730 malaria worldwide. All of these countries in Africa, progress using 0:13:47.770 --> 0:13:52.770 our standard tools has stalled. In those countries. We're going 0:13:52.850 --> 0:13:58.570 to need innovation in order to actually continue the downward 0:13:58.610 --> 0:14:02.810 trend and in fact, in some cases reverse what appears 0:14:02.850 --> 0:14:06.170 to be a rebound in the number of cases. The 0:14:06.250 --> 0:14:10.450 mosquitoes are rebounding in port because they've evolved resistance to 0:14:10.570 --> 0:14:16.090 overcome traditional methods of control. The major insecticide that we 0:14:16.250 --> 0:14:22.850 use to kill mosquitos. There's resistance in almost all mosquito populations, 0:14:22.890 --> 0:14:27.410 and so we anticipate that the need to have new 0:14:27.450 --> 0:14:31.410 insecticides is urgent, and without that we're unlikely to reach 0:14:31.410 --> 0:14:35.930 to eradication girls, particularly in sub Saharan Africa. So scientists 0:14:35.970 --> 0:14:40.410 are constantly imagining new solutions to save ecosystems and to 0:14:40.530 --> 0:14:49.010 save human lives. Could gene drives be the answer? Chapter 0:14:49.090 --> 0:14:55.410 two selfish genes? Instead of deploying poisons and viruses, what 0:14:55.530 --> 0:15:00.890 if we could just genetically reprogram pests to slow or 0:15:00.930 --> 0:15:06.170 even stop their reproduction. The strategy may sound simple, but 0:15:06.250 --> 0:15:10.210 it has a gaping hole. The logic of natural selection 0:15:10.370 --> 0:15:15.370 means the disadvantageous genes, ones that cause an organism to 0:15:15.410 --> 0:15:20.170 produce fewer offspring, should die out. Ah, But there's a 0:15:20.210 --> 0:15:25.810 loophole in theory. A gene could spread into population even 0:15:25.850 --> 0:15:29.890 if it hurts an organism's reproduction, if it could find 0:15:29.930 --> 0:15:33.690 a way to ensure that it gets inherited by most 0:15:33.770 --> 0:15:39.010 of the offspring. Could nature actually do that? Nature does 0:15:39.410 --> 0:15:45.370 such things often again, evolutionary ecologist Jim Collins well known 0:15:45.370 --> 0:15:49.130 example is a driving y chromosome in some species of mice, 0:15:49.570 --> 0:15:52.530 which converts a population into all males, and of course 0:15:52.530 --> 0:15:55.930 that population then would go extinct. It's one of those 0:15:56.770 --> 0:16:01.610 very interesting quirks of evolution in which you wind up 0:16:01.650 --> 0:16:05.410 with populations of all males basically blinking out of existence, 0:16:05.810 --> 0:16:08.250 and so you get one group can be converted into males, 0:16:08.250 --> 0:16:11.170 it goes extinct, but there are other groups that still 0:16:11.170 --> 0:16:14.490 have males and females and they'll continue on. When we 0:16:14.570 --> 0:16:17.490 think of how genes are passed on, we usually think 0:16:17.570 --> 0:16:22.930 about the laws of Mendelian inheritance, first recognized by Gregor Mendel, 0:16:23.250 --> 0:16:26.570 a friar and scientist who studied pea plants in the 0:16:26.610 --> 0:16:31.770 mid eighteen hundreds. Mendel figured out that in sexually reproducing species, 0:16:32.010 --> 0:16:35.450 each individual has two copies of each gene, one from 0:16:35.490 --> 0:16:39.050 their mother, one from their father. They pass on one 0:16:39.090 --> 0:16:41.970 of those two copies to each child, with the two 0:16:42.010 --> 0:16:45.890 copies each having a fifty fifty chance of being passed on. 0:16:46.770 --> 0:16:49.890 For example, imagine a gene that determines the sex of 0:16:49.930 --> 0:16:53.210 an offspring. If you have a sexually reproducing species that 0:16:53.290 --> 0:16:56.370 has males and females in it, a baby would be 0:16:56.850 --> 0:16:59.490 predicted to be a male fifty percent of the time 0:16:59.610 --> 0:17:02.090 female fifty percent of the time. But what if a 0:17:02.170 --> 0:17:07.410 gene naturally evolved that could cheat, could greedily stack the 0:17:07.530 --> 0:17:11.850 deck so that it gets inherited sixty eighty percent or 0:17:11.890 --> 0:17:15.850 even a hundred percent of the time, biologists referred to 0:17:15.890 --> 0:17:20.610 such selfish behavior as a gene drive. Party gene drive 0:17:20.690 --> 0:17:24.650 could do is changed that ratio as far as any 0:17:24.650 --> 0:17:27.170 particular genetic trade is concerned. So what was the first 0:17:27.170 --> 0:17:31.490 time anybody noticed the existence of a natural gene drive? 0:17:32.290 --> 0:17:35.570 They were described the very late eighteen hundreds, very early 0:17:35.650 --> 0:17:39.250 nineteen hundreds, so it's been known for a long time. 0:17:39.890 --> 0:17:44.010 Over the twentieth century, scientists discovered a vast array of 0:17:44.130 --> 0:17:46.970 gene drives in nature, but it was only in the 0:17:47.010 --> 0:17:50.530 beginning of this century that they began to seriously think 0:17:50.570 --> 0:17:54.610 about how they might harness the power of gene drives. 0:17:55.170 --> 0:18:00.090 Austin Burt was the one who laid out in principle 0:18:00.290 --> 0:18:05.690 the idea that if there were a way to control 0:18:06.650 --> 0:18:10.810 this natural process, then indeed you would have in your 0:18:10.850 --> 0:18:16.050 hands something that could control the gene frequency in populations. 0:18:16.570 --> 0:18:19.530 My name is Austin Burt, and I'm a professor of 0:18:19.570 --> 0:18:24.370 evolutionary genetics here at Imperial College, London. Austin's an expert 0:18:24.450 --> 0:18:29.610 in selfish genes, genes that cheat mandilion inheritance. Things that 0:18:29.650 --> 0:18:32.410 show gene drive or similar sorts of behavior, and all 0:18:32.450 --> 0:18:36.570 the other sorts of weird and wonderful genes out there 0:18:36.890 --> 0:18:40.130 are able to spread through populations not because they increase 0:18:40.370 --> 0:18:43.690 the survival or reproduction of the organism, but because they're 0:18:43.690 --> 0:18:48.050 distorting transmission to their own advantage. He became very interested 0:18:48.170 --> 0:18:52.170 in using gene drives for the benefit of public health. So, 0:18:52.330 --> 0:18:57.970 for example, in ades mosquitoes, which is the factor for 0:18:58.690 --> 0:19:01.410 a yellow fever and dany, there is an actually occurring 0:19:01.530 --> 0:19:05.690 selfish element on the Y chromosome, the male determining part 0:19:05.810 --> 0:19:10.050 of the genome, that gets into five percent or so 0:19:10.170 --> 0:19:13.290 of the progeny, and so it has the potential then 0:19:13.370 --> 0:19:16.810 to spread through a population, and as it does so, 0:19:16.970 --> 0:19:19.770 distort the sex ratio of the population to be more 0:19:19.770 --> 0:19:24.090 and more male biased. That's worth reiterating. A naturally occurring 0:19:24.210 --> 0:19:28.130 gene drive in mosquitoes turn ninety five percent of the 0:19:28.250 --> 0:19:32.490 male and that caught people's attention. Because male mosquitoes don't 0:19:32.530 --> 0:19:35.450 bite people, they don't transmit the disease, and so the 0:19:35.490 --> 0:19:37.570 idea was that you might be able to use that 0:19:37.610 --> 0:19:40.690 sort of elopment to control the diseases spread by those 0:19:40.730 --> 0:19:47.690 mosquitoes diseases like malaria. Unfortunately, gene drives in animals tend 0:19:47.690 --> 0:19:52.130 to use specialized tricks, many of which still aren't fully understood. 0:19:52.890 --> 0:19:56.090 The best gene drive to engineer would be based on 0:19:56.290 --> 0:20:01.250 simple principles, and you'd most likely find them in simple organisms. 0:20:02.010 --> 0:20:06.370 As luck would have it, That's what Austin studied. My 0:20:06.450 --> 0:20:11.730 first grant was to study the selfish genetic elements of yeasts. 0:20:13.970 --> 0:20:17.250 The best known gene drive in yeast exploits the fact 0:20:17.330 --> 0:20:21.330 that chromosomes come in pairs. So here's the trick. The 0:20:21.450 --> 0:20:26.210 gene drive occurs at a specific spot on a specific chromosome, 0:20:26.730 --> 0:20:30.730 and it encodes the instructions for an enzyme called a 0:20:30.810 --> 0:20:35.970 homing endonuclease. The sole purpose of that enzyme is to 0:20:36.090 --> 0:20:40.210 make a cut at the exact same spot on any 0:20:40.330 --> 0:20:44.010 other copy of the chromosome that doesn't already have the 0:20:44.050 --> 0:20:48.970 gene drive. When a cell detects that cut, it fills 0:20:49.010 --> 0:20:52.770 it in with the genetic information from the matching spot 0:20:52.850 --> 0:20:57.290 on the uncut chromosome, and presto chain show the cell 0:20:57.810 --> 0:21:01.210 inserts a copy of the gene drive into that spot 0:21:01.410 --> 0:21:07.410 on the chromosome. When I was reading about this, I thought, well, okay, 0:21:07.530 --> 0:21:12.530 so if that was actually then we could instead use 0:21:12.690 --> 0:21:15.650 that same sort of approach to change them to recognize 0:21:15.690 --> 0:21:19.610 mosquito sequences and then using that to knock out a 0:21:19.690 --> 0:21:23.210 gene that's essential for the survival or reproduction of the mosquito, 0:21:23.810 --> 0:21:27.450 and so suppress the population that way. In two thousand 0:21:27.490 --> 0:21:30.650 and three, Austin published a paper in the Proceedings of 0:21:30.650 --> 0:21:36.410 the Royal Society describing this brilliant idea. In principle, gene 0:21:36.490 --> 0:21:41.050 drives could be used to suppress a population, say decreasing 0:21:41.050 --> 0:21:45.850 the fertility of mosquitos, or to alter a population, say 0:21:46.170 --> 0:21:50.130 adding a gene that would prevent the malaria parasite from 0:21:50.410 --> 0:21:54.890 growing in the mosquito. But there was one hitch, the 0:21:54.970 --> 0:22:00.570 homing end. The nuclease in yeast recognizes only one specific 0:22:00.690 --> 0:22:06.050 DNA sequence. To engineer new gene drives, you'd need to 0:22:06.090 --> 0:22:10.970 be able to reprogram them to recognize different sequences. It 0:22:11.010 --> 0:22:14.450 was difficult to get the enzymes to be recognized new 0:22:14.490 --> 0:22:18.450 sequences to recognize mosquito sequences as opposed to E sequences, 0:22:18.850 --> 0:22:22.130 It would take another ten years before the solution emerged. 0:22:22.930 --> 0:22:26.410 It turned out to involve another system that accomplished the 0:22:26.490 --> 0:22:32.330 same thing in a very different way. The system was 0:22:32.410 --> 0:22:43.810 called Crisper. Chapter three, A Shining, Marvelous Future. Crisper is 0:22:43.850 --> 0:22:47.530 a kind of immune system that bacteria used to protect 0:22:47.530 --> 0:22:52.250 themselves against viruses. Crisper uses an enzyme to cut the 0:22:52.330 --> 0:22:56.610 virus's DNA. But what's amazing is that the enzyme doesn't 0:22:56.650 --> 0:23:02.450 have a fixed target. It's programmable. The bacteria create instructions 0:23:02.490 --> 0:23:06.930 based on past viral infections. The Crisper enzyme uses these 0:23:06.930 --> 0:23:10.610 instructions to search for matching the A sequence and then 0:23:10.770 --> 0:23:15.170 cuts it. It took twenty years and dozens of scientists 0:23:15.170 --> 0:23:18.930 around the world to understand exactly how Crisper works, but 0:23:19.050 --> 0:23:21.650 once they did, scientists figured out how to use its 0:23:21.650 --> 0:23:25.770 ability to target DNA sequences to create a technology to 0:23:25.930 --> 0:23:31.170 edit the genetic code inside living cells, from yeast to humans. 0:23:31.970 --> 0:23:35.810 Genome editing has made a huge splash, including the award 0:23:35.850 --> 0:23:39.770 of Nobel Prize last month to two scientists for their 0:23:39.850 --> 0:23:45.570 work on Crisper. Crisper has so many potential applications. Medical 0:23:45.650 --> 0:23:50.250 scientists realized that it held the prospect of fixing mutations 0:23:50.290 --> 0:23:55.010 in patients with severe diseases, and Austin Bert realized that 0:23:55.050 --> 0:23:59.330 this new technology could turn his idea of gene drives 0:23:59.330 --> 0:24:06.850 from dream into practical reality. Austin had been working for 0:24:07.170 --> 0:24:13.010 the last decade trying to engineer existing gene drives from 0:24:13.490 --> 0:24:16.650 organisms like yeast, and that was just a hideously complicated 0:24:16.690 --> 0:24:19.650 and difficult endeavor that wasn't getting all that far. Crisper 0:24:19.730 --> 0:24:23.570 was the perfect tool for enabling gene drive. This is 0:24:23.610 --> 0:24:27.130 biologist Kevin Esfeld, who was the first person to propose 0:24:27.170 --> 0:24:31.570 a specific design for a Crisper based gene drive. I'm 0:24:31.610 --> 0:24:34.210 an assistant professor at the MIT Media Lab, where I 0:24:34.330 --> 0:24:38.530 direct the Sculpting Evolution Group, and our job is to 0:24:38.570 --> 0:24:43.170 cultivate wisdom through ecological and evolutionary engineering. Kevin's interest in 0:24:43.250 --> 0:24:48.010 sculpting evolutions started early when he read Michael Crichton's nineteen 0:24:48.170 --> 0:24:52.330 ninety novel Jurassic Park. The mere notion that we might 0:24:52.330 --> 0:24:57.410 be able to resurrect dinosaurs through genetic engineering was just 0:24:57.490 --> 0:25:00.850 mind boggling. And even more so, there's this notion at 0:25:01.170 --> 0:25:08.050 the park was a synthetic ecosystem built to host creatures 0:25:08.090 --> 0:25:11.210 that live nowhere else us in the world. That's an 0:25:11.210 --> 0:25:17.330 incredible idea that we can potentially make our own ecosystems. 0:25:17.610 --> 0:25:20.370 How old were you when your address park? Oh, God, 0:25:20.570 --> 0:25:23.250 probably eight or nine. At a very young age, you 0:25:23.330 --> 0:25:24.810 might say, I knew what I wanted to do with 0:25:24.890 --> 0:25:30.010 my life. I wanted to understand how genetics made organisms 0:25:30.010 --> 0:25:32.690 and ecosystems the way they are, and I was interested 0:25:32.690 --> 0:25:34.970 in tinkering with them in order to better understand the 0:25:35.010 --> 0:25:37.850 answer to that question. Kevin remembers the moment when it 0:25:37.930 --> 0:25:41.090 dawned on him that Crisper would make it practical to 0:25:41.210 --> 0:25:46.490 engineer gene drives. He immediately read all of Austin's papers. 0:25:47.010 --> 0:25:49.290 The first day was purelation, thinking about all the amazing 0:25:49.330 --> 0:25:52.010 things you could do. You were thinking that applications already. 0:25:52.570 --> 0:25:56.650 One is human health, things like malarias just a semiasis dangey. 0:25:57.130 --> 0:26:00.170 It's spread by mosquito, lime disease, tick born illness, as mosquito, 0:26:00.170 --> 0:26:02.810 boorn illness, as parasites, you name it. Number two is 0:26:03.330 --> 0:26:07.850 environmental preservation, and then there's agriculture. Because instead of spraying 0:26:07.930 --> 0:26:10.090 nasty poisons on ours in order to get rid of 0:26:10.090 --> 0:26:11.810 the pests that eat them, how about we program the 0:26:11.810 --> 0:26:15.250 pests to dislike the taste. This is potentially a much 0:26:15.330 --> 0:26:21.890 more elegant way of solving ecological problems than poisons and bulldozers. 0:26:22.290 --> 0:26:26.850 In short, suppression gene drives aimed at suppressing the population 0:26:26.890 --> 0:26:30.650 of a dangerous or invasive species could provide a general 0:26:30.650 --> 0:26:36.570 approach to conquer terrible parasites and restore natural environments. To 0:26:36.610 --> 0:26:41.610 say that Kevin was excited would be an understatement. The 0:26:41.650 --> 0:26:45.370 possibilities of a shining, marvelous future were just exploding all 0:26:45.410 --> 0:26:48.930 around me like fireworks. Kevin published his proposal about how 0:26:48.930 --> 0:26:52.490 to build a crisper based gene drive in twenty fourteen. 0:26:53.370 --> 0:26:58.170 Within a year, scientific papers began reporting functioning gene drives, 0:26:58.410 --> 0:27:02.690 first in yeast, then fruit flies, and then in mosquitoes. 0:27:03.570 --> 0:27:07.410 Beyond Kevin's favorite applications, some people are thinking about gene 0:27:07.450 --> 0:27:10.330 drives as a way to help nate sure adapt rapidly 0:27:10.690 --> 0:27:14.010 to some of the devastating effects of climate change. My 0:27:14.090 --> 0:27:18.010 name's Natalie Chefler. I'm a molecular biologist, and I recently 0:27:18.050 --> 0:27:22.490 founded an initiative called Editing Nature, which tries to integrate 0:27:22.650 --> 0:27:26.810 diverse worldviews and perspectives to steer responsible development of genetic 0:27:26.930 --> 0:27:30.770 technologies for the environment. Natalie first became interested in gene 0:27:30.850 --> 0:27:33.970 drives because she was frustrated with the methods that were 0:27:34.010 --> 0:27:39.450 being used to get rid of specific invasive species. In Canada, 0:27:39.610 --> 0:27:43.810 where Natalie's from ash trees were disappearing at a frightening 0:27:43.890 --> 0:27:49.050 pace because they were being destroyed by invasive beetles originally 0:27:49.090 --> 0:27:53.850 from Asia. Ecologists had started considering ways to get rid 0:27:53.890 --> 0:27:57.490 of these beetles, and they pitched the idea of importing 0:27:57.610 --> 0:28:02.690 Russian wasps to prey on the Asian beetles. I was like, 0:28:02.730 --> 0:28:05.530 are you kidding me? This doesn't make Eddie sense and 0:28:05.650 --> 0:28:08.650 so and so I just started thinking that there must 0:28:08.690 --> 0:28:12.490 be bio tech options. That very year, Kevin Esvelt and 0:28:12.530 --> 0:28:15.890 his group had published reports on using crisper based gene 0:28:15.930 --> 0:28:18.810 drives to change wild species. And that was sort of 0:28:18.850 --> 0:28:22.290 the Aha moment where I thought, Okay, so people are 0:28:22.290 --> 0:28:25.650 looking at using genetic engineering to alter wild species. This 0:28:25.850 --> 0:28:29.810 is really exciting because it could provide a solution for 0:28:29.850 --> 0:28:34.290 these really huge challenges that we're facing. Among those challenges, 0:28:34.450 --> 0:28:38.250 Natalie points to what's happening to coral reefs. So we're 0:28:38.250 --> 0:28:41.130 seeing a huge decline in coral reef health right now, 0:28:41.490 --> 0:28:45.330 in large part because ocean temperatures are rising. Oceans are 0:28:45.330 --> 0:28:48.890 becoming more acidic and that's causing a lot of stress 0:28:48.930 --> 0:28:53.370 to the coral. It's happening really quickly and pretty extensively. 0:28:54.130 --> 0:28:57.290 White of coral reefs matter. I always see them as 0:28:57.290 --> 0:28:59.690 it was like the forests of the sea. So they 0:28:59.770 --> 0:29:04.490 create huge amount of habitat for many marine fish. Many 0:29:04.530 --> 0:29:07.490 people's livelihoods depend on the fish that depend on coral reef, 0:29:08.130 --> 0:29:11.330 and so there's been estimates in the trillions and trillions 0:29:11.330 --> 0:29:13.410 of dollars that would be lost if the coral were 0:29:13.450 --> 0:29:15.330 to continue to decline at the rates that they do, 0:29:15.730 --> 0:29:19.010 So losing all the coral would be like losing all 0:29:19.010 --> 0:29:23.050 the forests in a way. That's somehow I think about it. 0:29:23.090 --> 0:29:28.530 In contrast to suppression gene drives, Natalie thinks that alteration 0:29:28.650 --> 0:29:33.610 gene drives, ones that would spread beneficial genes throughout a population, 0:29:34.130 --> 0:29:38.410 could make some coals more resilient to climate change. And 0:29:38.490 --> 0:29:40.810 there is research starting to come out showing that certain 0:29:41.490 --> 0:29:44.370