0:00:01.163,0:00:02.291 Hi everyone. 0:00:02.291,0:00:05.932 I would like to introduce you to Laika. 0:00:05.932,0:00:10.825 To most of us, Laika is simply[br]a very cute pig. 0:00:10.825,0:00:17.182 However, to hundreds of thousands[br]of patients in need of a lifesaving organ, 0:00:17.182,0:00:20.061 Laika is a symbol of hope. 0:00:21.160,0:00:24.264 You see, ever since the 1970s, 0:00:24.264,0:00:27.654 when organ transplants[br]became a real option 0:00:27.654,0:00:31.844 for patients with kidney failure[br]and other organ diseases, 0:00:31.844,0:00:35.022 organ supply has been an issue. 0:00:35.022,0:00:36.979 Over the last few decades, 0:00:36.979,0:00:42.306 the issue only worsened as organ demand[br]has exponentially increased. 0:00:43.141,0:00:45.725 Currently in the US, 0:00:45.725,0:00:50.024 there are close to 115,000 patients 0:00:50.024,0:00:53.738 in need of a lifesaving organ transplant. 0:00:53.738,0:00:55.580 By the end of my talk, 0:00:55.580,0:01:00.337 one more patient[br]will be added to this list. 0:01:00.337,0:01:04.575 Today, about 100 people[br]will get a new organ, 0:01:04.575,0:01:08.423 a chance to start their life anew, 0:01:08.423,0:01:10.695 and yet by the end of today, 0:01:10.695,0:01:13.703 20 others will die waiting. 0:01:14.462,0:01:16.730 The situation is heartbreaking 0:01:16.730,0:01:19.939 for patients, for their families, 0:01:19.939,0:01:23.518 and for the doctors who want to do more. 0:01:24.293,0:01:26.187 In some parts of the world, 0:01:26.187,0:01:30.510 the situation also becomes[br]a disturbing social issue. 0:01:30.510,0:01:32.309 In Asia, for example, 0:01:32.309,0:01:36.485 media outlets reported that[br]desperate patients 0:01:36.485,0:01:38.741 are obtaining organs 0:01:38.741,0:01:41.862 from the cruel black market. 0:01:41.862,0:01:47.373 It is clear that a solution[br]is needed to this crisis. 0:01:47.373,0:01:50.433 Human lives are at stake. 0:01:51.417,0:01:54.466 As a biologist and a geneticist, 0:01:54.466,0:01:58.453 it has become my mission[br]to help solve this problem. 0:01:58.987,0:02:04.070 Today, I am optimistic to say[br]that we are on our way there, 0:02:04.070,0:02:05.845 thanks to Laika. 0:02:05.845,0:02:08.192 Using gene editing technology, 0:02:08.192,0:02:14.006 it's now possible to exclusively create[br]a human transplantable organ 0:02:14.006,0:02:16.928 that can be safely grown in pigs. 0:02:18.135,0:02:22.437 Before we jump into the incredible[br]science that makes it happen, 0:02:22.437,0:02:27.128 let's have a better understanding[br]what xenotransplantation is. 0:02:27.441,0:02:32.252 It's a process of transplanting[br]animal organs into humans. 0:02:32.252,0:02:35.785 You may want to ask, why pig organs? 0:02:35.785,0:02:40.612 Because some pigs carry organs[br]with similar size and physiology 0:02:40.612,0:02:42.471 to human organs. 0:02:42.471,0:02:45.027 Over the last half a century, 0:02:45.027,0:02:49.855 pioneers of transplantation[br]have tried hard to make it happen, 0:02:49.855,0:02:53.250 but with limited to no success. 0:02:53.472,0:02:54.906 Why is that? 0:02:54.906,0:02:58.515 Two fundamental hurdles stood in the way. 0:02:58.515,0:03:01.695 First is a problem of rejection. 0:03:01.695,0:03:05.558 When our immune system[br]sees a new organ as foreign, 0:03:05.558,0:03:07.754 it will reject it. 0:03:07.754,0:03:12.322 Second, and this one is specific[br]to the organs from the pig, 0:03:12.322,0:03:17.502 every pig carries a virus[br]that has been ?? to the pig, 0:03:17.502,0:03:20.157 but can be transmitted into humans. 0:03:20.157,0:03:24.569 It is called the porcine[br]endogenous retrovirus (PERV), 0:03:24.569,0:03:30.160 and this virus has the potential[br]to cause a viral epidemic 0:03:30.160,0:03:32.647 similar to HIV. 0:03:32.647,0:03:37.098 Without an effective way[br]to address these issues, 0:03:37.098,0:03:43.909 the field of xenotransplantation[br]has been on hold for more than one decade. 0:03:43.909,0:03:48.383 Little progress has been made, until now. 0:03:49.719,0:03:54.160 Let me share with you[br]how I got here today with Laika. 0:03:54.538,0:03:58.638 My journey started from[br]?? Mountain in China. 0:03:58.638,0:04:03.031 That is the place ?? described[br]in a lot of legendary stories, 0:04:03.031,0:04:06.088 like the "Crouching Tiger, Hidden Dragon." 0:04:06.088,0:04:09.208 That is the place I call home. 0:04:09.208,0:04:10.935 Growing up in the mountain, 0:04:10.935,0:04:14.967 I started to have a strong[br]connection with nature. 0:04:14.967,0:04:18.033 This is me when I was seven years old 0:04:18.033,0:04:21.529 standing in front of[br]an ancient Buddhist temple 0:04:21.529,0:04:23.554 with a monkey on my shoulder. 0:04:23.554,0:04:26.997 I still vividly remember[br]how my friends and I 0:04:26.997,0:04:30.263 would toss the peanuts around[br]to distract the monkeys 0:04:30.263,0:04:33.641 so that we could cross[br]to hike through the valley. 0:04:34.024,0:04:35.605 I loved nature. 0:04:35.605,0:04:38.457 When it was time[br]to choose a field of study, 0:04:38.457,0:04:44.002 I chose to study biology[br]at Peking University in Beijing. 0:04:44.002,0:04:46.522 However, the more I learned, 0:04:46.522,0:04:48.805 the more questions I had. 0:04:48.805,0:04:53.314 How could our genetic makeup[br]be so similar to animals, 0:04:53.314,0:04:56.252 and yet we look so different? 0:04:56.252,0:05:00.871 How is our immune system capable[br]of fighting off so many pathogens 0:05:00.871,0:05:04.403 but smart enough not to attack ourselves. 0:05:04.596,0:05:08.186 Questions like this tormented me. 0:05:08.186,0:05:12.187 I know it sounds nerdy,[br]but you know I'm a scientist. 0:05:12.187,0:05:17.471 After college, I decided[br]I didn't want to just ask the questions, 0:05:17.471,0:05:21.888 I wanted to answer them, so I did. 0:05:21.888,0:05:29.404 In 2008, I was lucky enough to be accepted[br]into the PhD program at Harvard University 0:05:29.404,0:05:31.940 and worked with Dr. George Church. 0:05:32.222,0:05:36.643 While working in Church's lab,[br]I started to learn and experiment with 0:05:36.643,0:05:39.514 the genetic makeup of mammals. 0:05:39.514,0:05:42.169 Among all the experiments, 0:05:42.169,0:05:45.800 one particular one[br]took me closer to Laika. 0:05:45.800,0:05:51.728 In 2013, my colleagues and I[br]made changes in a human cell 0:05:51.728,0:05:54.861 using a tool you may have heard about 0:05:54.861,0:05:56.116 called CRISPR. 0:05:56.116,0:05:59.608 We were one of the first two groups 0:05:59.608,0:06:04.483 to report the successful use[br]of such a tool in changing our DNA. 0:06:04.483,0:06:09.066 It was an exciting moment[br]in scientific discovery. 0:06:09.066,0:06:13.545 The gene-editing tool CRISPR[br]has two components. 0:06:13.545,0:06:16.775 It has a scissor called the ??, 0:06:16.775,0:06:20.251 and what is called a guide RNA. 0:06:20.251,0:06:24.376 Think about it as a genetic scissors[br]with a microscope. 0:06:24.376,0:06:27.661 The microscope is a guide RNA, 0:06:27.661,0:06:31.539 which brings the scissors[br]to the place we want to cut 0:06:31.539,0:06:33.494 and says, "Here it is," 0:06:33.494,0:06:38.910 and the ?? CRISPR just cuts[br]and repairs the DNA in the way we want. 0:06:39.951,0:06:43.197 Shortly after we reported our study, 0:06:43.197,0:06:49.025 physicians at Mass General Hospital[br]were intrigued by the medical applications 0:06:49.025,0:06:50.764 of our research. 0:06:50.764,0:06:54.130 They reached out to us, 0:06:54.130,0:06:56.401 and together, we began to see[br]the potential to use CRISPR 0:06:56.401,0:07:00.227 to solve the organ shortage crisis. 0:07:00.227,0:07:01.835 How do we do it? 0:07:01.835,0:07:06.297 It is simple, yet very complex. 0:07:06.297,0:07:11.349 We started by making changes[br]in a pig's cell to make virus-free 0:07:11.349,0:07:15.273 and human-immune-compatible. 0:07:15.273,0:07:19.918 The nucleus of that cell[br]is then implanted into a pig egg 0:07:19.918,0:07:22.944 and allowed to divide into an embryo. 0:07:22.944,0:07:28.484 The resulting embryo is then placed[br]into the uterus of a surrogate mother 0:07:28.484,0:07:31.070 and allowed to divide into a pig. 0:07:31.070,0:07:34.030 Basically, it's a process of cloning. 0:07:34.030,0:07:37.947 The piglet then carries organs[br]whose genetic makeup 0:07:37.947,0:07:41.266 hopefully wouldn't be rejected[br]by the human immune system. 0:07:42.914,0:07:49.711 In 2015, our team decided to tackle[br]the viral transmission problem first. 0:07:49.711,0:07:58.330 We wanted to take out all 62 copies[br]of the PERV virus from the pig genome, 0:07:58.330,0:08:02.495 but at the time, it was[br]nearly mission impossible. 0:08:02.495,0:08:05.348 Even with CRISPR, 0:08:05.348,0:08:08.938 we could only do one or two[br]modifications within a cell. 0:08:08.938,0:08:15.475 The record for number of modifications[br]we can do in a particular cell was five. 0:08:15.475,0:08:21.382 We had to increase the through-put[br]by more than tenfold to achieve that. 0:08:21.382,0:08:25.354 With very careful design[br]and hundreds of trials, 0:08:25.354,0:08:29.313 we successfully took out all the virus, 0:08:29.313,0:08:30.589 broke the record. 0:08:30.589,0:08:34.714 More importantly, our studies showed[br]that we could eliminate 0:08:34.714,0:08:37.773 the possibility of this dangerous virus 0:08:37.773,0:08:40.547 being transmitted into humans. 0:08:41.346,0:08:45.706 Last year, with a modified cell[br]and cloning technology, 0:08:45.706,0:08:50.478 our startup, eGenesis, produced Laika, 0:08:50.478,0:08:55.496 the first pig of its kind[br]born without PERV. 0:08:55.496,0:08:59.520 (Applause) 0:08:59.709,0:09:07.276 Laika represents the first critical step[br]in establishing safe xenotransplantation. 0:09:07.276,0:09:09.529 It is also a platform 0:09:09.529,0:09:12.251 that we can do further[br]genetic modification on 0:09:12.251,0:09:15.169 to solve the immunology problem. 0:09:15.169,0:09:20.208 Since then, we have created[br]more than 30 pigs without PERV, 0:09:20.208,0:09:26.295 and they may be the most advanced[br]geno-modified animal living on Earth. 0:09:26.295,0:09:29.762 We named Laika after the Soviet dog 0:09:29.762,0:09:33.620 who was the first animal[br]to orbit the Earth. 0:09:33.620,0:09:36.812 We hope Laika and her siblings 0:09:36.812,0:09:43.694 can lead us into a new frontier[br]of science and medicine. 0:09:43.694,0:09:48.801 Imagine a world where patients[br]who suffer from liver failure 0:09:48.801,0:09:51.739 can be saved with a new liver 0:09:51.739,0:09:54.923 without having to wait for a donation 0:09:54.923,0:09:57.848 or another human to die. 0:09:57.848,0:10:01.917 Imagine a world[br]where people with diabetes 0:10:01.917,0:10:05.775 do not have to rely[br]on insulin after every meal 0:10:05.775,0:10:09.956 because we can provide them[br]with good pancreatic cells 0:10:09.956,0:10:12.927 that can produce insulin on their own. 0:10:12.927,0:10:17.841 And imagine a world[br]where patients with kidney failure 0:10:17.841,0:10:22.773 do not have the face[br]the burden of dialysis. 0:10:22.773,0:10:26.394 We are striving to create that world, 0:10:26.394,0:10:29.994 a world without organ shortage. 0:10:29.994,0:10:34.410 We finally have the tool[br]to tackle the problem 0:10:34.410,0:10:36.083 we could never tackle before, 0:10:36.083,0:10:40.132 and Laika is just[br]the beginning of our journey. 0:10:40.132,0:10:43.881 We have to be very humble[br]in front of nature, 0:10:43.881,0:10:46.560 because there are more issues[br]to be addressed, 0:10:46.560,0:10:48.390 including immunology 0:10:48.390,0:10:53.116 and things we couldn't even[br]anticipate at this point. 0:10:53.116,0:10:59.179 However, it is our responsibility[br]to translate the cutting edge science 0:10:59.179,0:11:00.598 into medicine to save the lives[br]of all the patients who are waiting. 0:11:00.598,0:11:07.029 Thank you very much. 0:11:07.029,0:11:09.121 (Applause) 0:11:15.994,0:11:21.901 Chris Anderson: I mean, Luhan,[br]this is extraordinary work here. 0:11:21.901,0:11:23.956 Come forward. 0:11:23.956,0:11:28.427 So what's the next steps here?[br]You've got rid of the virus. 0:11:28.427,0:11:31.280 The next steps involve[br]trying to get to the point 0:11:31.280,0:11:34.504 where a human body[br]won't reject a transplant. 0:11:34.504,0:11:36.402 What's involved in solving that? 0:11:36.402,0:11:39.664 Luhan Yang: It's a very[br]complicated process. 0:11:39.664,0:11:44.210 So we need to take out[br]the ?? of the pigs. 0:11:44.210,0:11:47.684 In addition, we can learn[br]a lot from cancer. 0:11:47.684,0:11:51.793 How can cancer invade[br]or circumvent our immune system 0:11:51.793,0:11:55.606 so that we can utilize the trick of cancer 0:11:55.606,0:11:58.999 and implement that on the pig organ 0:11:58.999,0:12:03.463 to fool our immune system[br]to not attack the organ. 0:12:03.463,0:12:07.425 CA: When would you estimate,[br]when do you hope, 0:12:07.425,0:12:11.480 that the first successful[br]transplant would happen? 0:12:11.480,0:12:15.336 LY: It would be irresponsible for me[br]to give you any number. 0:12:15.336,0:12:19.025 CA: We're at TED.[br]We're always irresponsible. 0:12:19.025,0:12:22.165 LY: But we are working day and night[br]trying to make this happen 0:12:22.165,0:12:23.716 for the patients. 0:12:23.716,0:12:27.281 CA: So not even, you won't say[br]that you think it could happen 0:12:27.281,0:12:29.607 within a decade or within[br]five years or something? 0:12:29.607,0:12:32.311 LY: For sure we hope it happens[br]within one decade. 0:12:32.311,0:12:34.186 (Laughter) 0:12:34.186,0:12:38.548 CA: So there's a lot of people here[br]who would be very, very excited at that, 0:12:38.548,0:12:39.397 and the potential is extraordinary. 0:12:39.397,0:12:40.995 There will be some other[br]people here who are going, 0:12:40.995,0:12:43.245 "That pig is too cute. 0:12:43.245,0:12:47.830 Humans shouldn't be exploiting[br]something so cute for our benefit." 0:12:47.830,0:12:51.446 Do you have any response to that? 0:12:51.446,0:12:55.524 LY: Yeah, sure. 0:12:55.524,0:12:57.696 So imagine one pig can save[br]eight people's lives. 0:12:57.696,0:13:01.144 In addition, similar to human donation, 0:13:01.144,0:13:03.464 if we only harvest[br]one kidney from the pig, 0:13:03.464,0:13:05.493 the pig can still be alive, 0:13:05.493,0:13:09.572 so we are very mindful about the issues, 0:13:09.572,0:13:13.937 but I think our goal is just to address[br]the unmet medical need 0:13:13.937,0:13:16.883 for those patients and their families. 0:13:16.883,0:13:20.344 CA: Plus, no one can say that to you[br]if they eat bacon, right? 0:13:20.344,0:13:22.714 LY: That's a good point. 0:13:22.714,0:13:23.950 (Laughter) 0:13:23.950,0:13:26.212 CA: Luhan, thank you so much.[br]LY: Thank you so much. 0:13:26.212,0:13:27.892 (Applause)