1 00:00:00,840 --> 00:00:02,056 Hi everyone. 2 00:00:02,080 --> 00:00:04,560 I would like to introduce you to Laika. 3 00:00:05,680 --> 00:00:09,880 To most of us, Laika is simply a very cute pig. 4 00:00:10,800 --> 00:00:17,336 However, to hundreds of thousands of patients in need of a lifesaving organ 5 00:00:17,360 --> 00:00:19,640 Laika is a symbol of hope. 6 00:00:20,960 --> 00:00:24,056 You see, ever since the 1970s, 7 00:00:24,080 --> 00:00:27,376 when organ transplants became a real option 8 00:00:27,400 --> 00:00:31,616 for patients with kidney failure and other organ diseases, 9 00:00:31,640 --> 00:00:34,240 organ supply has been an issue. 10 00:00:34,920 --> 00:00:36,816 Over the last few decades, 11 00:00:36,840 --> 00:00:41,880 the issue only worsened as organ demand has exponentially increased. 12 00:00:43,400 --> 00:00:45,696 Currently in the US, 13 00:00:45,720 --> 00:00:49,896 there are close to 115,000 patients 14 00:00:49,920 --> 00:00:52,680 in need of a lifesaving organ transplant. 15 00:00:53,520 --> 00:00:55,336 By the end of my talk, 16 00:00:55,360 --> 00:00:59,120 one more patient will be added to this list. 17 00:01:00,120 --> 00:01:04,495 Today, about 100 people will get a new organ, 18 00:01:04,519 --> 00:01:07,336 a chance to start their life anew, 19 00:01:07,360 --> 00:01:10,336 and yet by the end of today, 20 00:01:10,360 --> 00:01:12,840 20 others will die waiting. 21 00:01:14,240 --> 00:01:16,736 The situation is heartbreaking 22 00:01:16,760 --> 00:01:19,656 for patients, for their families 23 00:01:19,680 --> 00:01:22,680 and for the doctors who want to do more. 24 00:01:24,000 --> 00:01:25,936 In some parts of the world, 25 00:01:25,960 --> 00:01:29,560 the situation also becomes a disturbing social issue. 26 00:01:30,120 --> 00:01:32,096 In Asia, for example, 27 00:01:32,120 --> 00:01:36,176 media outlets reported that desperate patients 28 00:01:36,200 --> 00:01:40,120 are obtaining organs from the cruel black market. 29 00:01:41,600 --> 00:01:47,016 It is clear that a solution is needed to this crisis. 30 00:01:47,040 --> 00:01:49,600 Human lives are at stake. 31 00:01:51,160 --> 00:01:54,216 As a biologist and a geneticist, 32 00:01:54,240 --> 00:01:57,920 it has become my mission to help solve this problem. 33 00:01:58,760 --> 00:02:03,776 Today, I am optimistic to say that we are on our way there, 34 00:02:03,800 --> 00:02:05,000 thanks to Laika. 35 00:02:05,600 --> 00:02:07,936 Using gene editing technology, 36 00:02:07,960 --> 00:02:13,816 it's now possible to exquisitely create a human-transplantable organ 37 00:02:13,840 --> 00:02:16,400 that can be safely grown in pigs. 38 00:02:17,920 --> 00:02:22,176 Before we jump into the incredible science that makes it happen, 39 00:02:22,200 --> 00:02:26,600 let's have a better understanding what xenotransplantation is. 40 00:02:27,120 --> 00:02:31,600 It's a process of transplanting animal organs into humans. 41 00:02:32,480 --> 00:02:35,496 You may want to ask, why pig organs? 42 00:02:35,520 --> 00:02:40,336 Because some pigs carry organs with similar size and physiology 43 00:02:40,360 --> 00:02:41,560 to human organs. 44 00:02:42,280 --> 00:02:44,696 Over the last half a century, 45 00:02:44,720 --> 00:02:49,576 pioneers of transplantation have tried hard to make it happen, 46 00:02:49,600 --> 00:02:52,480 but with limited to no success. 47 00:02:53,080 --> 00:02:54,280 Why is that? 48 00:02:54,880 --> 00:02:57,640 Two fundamental hurdles stood in the way. 49 00:02:58,240 --> 00:03:01,416 First is a problem of rejection. 50 00:03:01,440 --> 00:03:05,256 When our immune system sees a new organ as foreign, 51 00:03:05,280 --> 00:03:06,520 it will reject it. 52 00:03:07,400 --> 00:03:11,720 Second, and this one is specific to the organs from the pig, 53 00:03:12,760 --> 00:03:17,176 every pig carries a virus that has been native to the pig, 54 00:03:17,200 --> 00:03:19,856 but can be transmitted into humans. 55 00:03:19,880 --> 00:03:25,376 It is called the porcine endogenous retrovirus (PERV) 56 00:03:25,400 --> 00:03:31,400 and this virus has the potential to cause a viral epidemic similar to HIV. 57 00:03:32,280 --> 00:03:37,056 Without an effective way to address these issues, 58 00:03:37,080 --> 00:03:42,680 the field of xenotransplantation has been on hold for more than one decade. 59 00:03:43,600 --> 00:03:47,680 Little progress has been made, until now. 60 00:03:49,480 --> 00:03:53,160 Let me share with you how I got here today with Laika. 61 00:03:54,280 --> 00:03:58,296 My journey started from ?? Mountain in China. 62 00:03:58,320 --> 00:04:02,736 That is the place well described in a lot of legendary stories, 63 00:04:02,760 --> 00:04:05,400 like the "Crouching Tiger, Hidden Dragon." 64 00:04:05,840 --> 00:04:08,160 That is the place I call home. 65 00:04:08,920 --> 00:04:10,656 Growing up in the mountain, 66 00:04:10,680 --> 00:04:13,760 I started to have a strong connection with nature. 67 00:04:14,680 --> 00:04:17,736 This is me when I was seven years old 68 00:04:17,760 --> 00:04:21,176 standing in front of an ancient Buddhist temple 69 00:04:21,200 --> 00:04:23,216 with a monkey on my shoulder. 70 00:04:23,240 --> 00:04:26,816 I still vividly remember how my friends and I 71 00:04:26,840 --> 00:04:30,016 would toss peanuts around to distract the monkeys 72 00:04:30,040 --> 00:04:32,720 so that we could cross to hike through the valley. 73 00:04:33,840 --> 00:04:35,336 I loved nature. 74 00:04:35,360 --> 00:04:38,216 When it was time to choose a field of study, 75 00:04:38,240 --> 00:04:42,240 I chose to study biology at Peking University in Beijing. 76 00:04:43,760 --> 00:04:46,256 However, the more I learned, 77 00:04:46,280 --> 00:04:47,600 the more questions I had. 78 00:04:48,520 --> 00:04:53,056 How could our genetic makeup be so similar to animals, 79 00:04:53,080 --> 00:04:55,000 and yet we look so different? 80 00:04:55,920 --> 00:05:00,776 How is our immune system capable of fighting off so many pathogens 81 00:05:00,800 --> 00:05:03,520 but smart enough not to attack ourselves. 82 00:05:04,280 --> 00:05:06,800 Questions like this tormented me. 83 00:05:07,880 --> 00:05:10,720 I know it sounds nerdy, but you know I'm a scientist. 84 00:05:12,000 --> 00:05:17,256 After college, I decided I didn't want to just ask the questions, 85 00:05:17,280 --> 00:05:20,440 I wanted to answer them, so I did. 86 00:05:21,560 --> 00:05:25,616 In 2008, I was lucky enough to be accepted 87 00:05:25,640 --> 00:05:29,176 into the PhD program at Harvard University 88 00:05:29,200 --> 00:05:31,280 and worked with Dr. George Church. 89 00:05:31,920 --> 00:05:33,656 While working in Church's lab, 90 00:05:33,680 --> 00:05:38,360 I started to learn and experiment with the genetic makeup of mammals. 91 00:05:39,200 --> 00:05:41,456 Among all the experiments, 92 00:05:41,480 --> 00:05:44,680 one particular one took me closer to Laika. 93 00:05:45,520 --> 00:05:51,456 In 2013, my colleagues and I made changes in a human cell 94 00:05:51,480 --> 00:05:53,936 using a tool you may have heard about 95 00:05:53,960 --> 00:05:55,496 called CRISPR. 96 00:05:55,520 --> 00:05:58,736 We were one of the first two groups 97 00:05:58,760 --> 00:06:04,136 to report the successful use of such a tool in changing our DNA. 98 00:06:04,160 --> 00:06:07,680 It was an exciting moment in scientific discovery. 99 00:06:08,800 --> 00:06:13,136 The gene-editing tool CRISPR has two components. 100 00:06:13,160 --> 00:06:16,656 It has a scissor called the enzyme CRISPR 101 00:06:16,680 --> 00:06:19,360 and what is called a guide RNA. 102 00:06:19,920 --> 00:06:24,056 Think about it as genetic scissors with a microscope. 103 00:06:24,080 --> 00:06:27,176 The microscope is a guide RNA, 104 00:06:27,200 --> 00:06:31,216 which brings the scissors to the place we want to cut 105 00:06:31,240 --> 00:06:33,256 and says, "Here it is," 106 00:06:33,280 --> 00:06:38,520 and the enzyme CRISPR just cuts and repairs the DNA in the way we want. 107 00:06:39,720 --> 00:06:42,936 Shortly after we reported our study, 108 00:06:42,960 --> 00:06:48,896 physicians at Mass General Hospital were intrigued by the medical applications 109 00:06:48,920 --> 00:06:50,496 of our research. 110 00:06:50,520 --> 00:06:52,016 They reached out to us, 111 00:06:52,040 --> 00:06:56,136 and together, we began to see the potential to use CRISPR 112 00:06:56,160 --> 00:06:58,760 to solve the organ shortage crisis. 113 00:06:59,840 --> 00:07:01,456 How do we do it? 114 00:07:01,480 --> 00:07:04,600 It is simple, yet very complex. 115 00:07:06,080 --> 00:07:12,096 We started by making changes in a pig's cell to make it virus-free 116 00:07:12,120 --> 00:07:14,896 and human-immune-compatible. 117 00:07:14,920 --> 00:07:19,696 The nucleus of that cell is then implanted into a pig egg 118 00:07:19,720 --> 00:07:22,616 and allowed to divide into an embryo. 119 00:07:22,640 --> 00:07:27,936 The resulting embryo is then placed into the uterus of a surrogate mother 120 00:07:27,960 --> 00:07:30,000 and allowed to divide into a pig. 121 00:07:30,680 --> 00:07:33,040 Basically, it's a process of cloning. 122 00:07:33,760 --> 00:07:37,616 The piglet then carries organs whose genetic makeup 123 00:07:37,640 --> 00:07:41,240 hopefully wouldn't be rejected by the human immune system. 124 00:07:42,960 --> 00:07:49,376 In 2015, our team decided to tackle the viral transmission problem first. 125 00:07:49,400 --> 00:07:55,576 We wanted to take out all 62 copies of the PERV virus 126 00:07:55,600 --> 00:07:57,000 from the pig genome, 127 00:07:58,200 --> 00:08:02,336 but at the time, it was nearly mission impossible. 128 00:08:02,360 --> 00:08:03,776 Even with CRISPR, 129 00:08:03,800 --> 00:08:08,616 we could only do one or two modifications within a cell. 130 00:08:08,640 --> 00:08:15,176 The record for number of modifications we can do in a particular cell was five. 131 00:08:15,200 --> 00:08:20,440 We had to increase the throughput by more than tenfold to achieve that. 132 00:08:21,400 --> 00:08:25,056 With very careful design and hundreds of trials, 133 00:08:25,080 --> 00:08:28,296 we successfully took out all the virus, 134 00:08:28,320 --> 00:08:29,896 broke the record. 135 00:08:29,920 --> 00:08:32,376 More importantly, our studies showed 136 00:08:32,400 --> 00:08:37,456 that we could eliminate the possibility of this dangerous virus 137 00:08:37,480 --> 00:08:39,799 being transmitted into humans. 138 00:08:41,080 --> 00:08:45,456 Last year, with a modified cell and cloning technology, 139 00:08:45,480 --> 00:08:49,320 our startup, eGenesis, produced Laika, 140 00:08:50,160 --> 00:08:54,640 the first pig of its kind born without PERV. 141 00:08:55,480 --> 00:08:59,216 (Applause) 142 00:08:59,240 --> 00:09:03,216 Laika represents the first critical step 143 00:09:03,240 --> 00:09:06,976 in establishing safe xenotransplantation. 144 00:09:07,000 --> 00:09:08,896 It is also a platform 145 00:09:08,920 --> 00:09:11,896 that we can do further genetic modification on 146 00:09:11,920 --> 00:09:14,120 to solve the immunology problem. 147 00:09:14,760 --> 00:09:19,856 Since then, we have created more than 30 pigs without PERV, 148 00:09:19,880 --> 00:09:25,480 and they may be the most advanced geno-modified animal living on Earth. 149 00:09:26,400 --> 00:09:29,696 We named Laika after the Soviet dog 150 00:09:29,720 --> 00:09:33,040 who was the first animal to orbit the Earth. 151 00:09:33,600 --> 00:09:36,576 We hope Laika and her siblings 152 00:09:36,600 --> 00:09:41,400 can lead us into a new frontier of science and medicine. 153 00:09:43,360 --> 00:09:48,496 Imagine a world where patients who suffer from liver failure 154 00:09:48,520 --> 00:09:51,176 can be saved with a new liver 155 00:09:51,200 --> 00:09:54,256 without having to wait for a donation 156 00:09:54,280 --> 00:09:56,080 or another human to die. 157 00:09:57,600 --> 00:10:01,696 Imagine a world where people with diabetes 158 00:10:01,720 --> 00:10:05,456 do not have to rely on insulin after every meal 159 00:10:05,480 --> 00:10:09,576 because we can provide them with good pancreatic cells 160 00:10:09,600 --> 00:10:11,880 that can produce insulin on their own. 161 00:10:12,600 --> 00:10:17,576 And imagine a world where patients with kidney failure 162 00:10:17,600 --> 00:10:21,280 do not have to face the burden of dialysis. 163 00:10:22,320 --> 00:10:26,056 We are striving to create that world, 164 00:10:26,080 --> 00:10:28,880 a world without organ shortage. 165 00:10:29,720 --> 00:10:33,456 We finally have the tool to tackle the problem 166 00:10:33,480 --> 00:10:35,616 we could never tackle before, 167 00:10:35,640 --> 00:10:38,920 and Laika is just the beginning of our journey. 168 00:10:40,040 --> 00:10:43,576 We have to be very humble in front of nature, 169 00:10:43,600 --> 00:10:46,216 because there are more issues to be addressed, 170 00:10:46,240 --> 00:10:47,856 including immunology 171 00:10:47,880 --> 00:10:51,840 and things we couldn't even anticipate at this point. 172 00:10:52,760 --> 00:10:58,896 However, it is our responsibility to translate the cutting-edge science 173 00:10:58,920 --> 00:11:04,240 into medicine to save the lives of all the patients who are waiting. 174 00:11:05,480 --> 00:11:06,736 Thank you very much. 175 00:11:06,760 --> 00:11:11,600 (Applause) 176 00:11:17,800 --> 00:11:21,296 Chris Anderson: I mean, Luhan, this is extraordinary work here. 177 00:11:21,320 --> 00:11:22,520 Come forward. 178 00:11:23,640 --> 00:11:28,056 So what's the next steps here? You've got rid of the virus. 179 00:11:28,080 --> 00:11:30,416 The next steps involve trying to get to the point 180 00:11:30,440 --> 00:11:34,216 where a human body won't reject a transplant. 181 00:11:34,240 --> 00:11:36,040 What's involved in solving that? 182 00:11:37,160 --> 00:11:39,416 Luhan Yang: It's a very complicated process. 183 00:11:39,440 --> 00:11:43,896 So we need to take out the antigen of the pigs. 184 00:11:43,920 --> 00:11:47,336 In addition, we can learn a lot from cancer. 185 00:11:47,360 --> 00:11:51,536 How can cancer invade or circumvent our immune system 186 00:11:51,560 --> 00:11:56,016 so that we can utilize the trick of cancer 187 00:11:56,040 --> 00:11:58,376 and implement that on the pig organ 188 00:11:58,400 --> 00:12:01,480 to fool our immune system to not attack the organ. 189 00:12:03,680 --> 00:12:07,056 CA: When would you estimate, when do you hope 190 00:12:07,080 --> 00:12:10,400 that the first successful transplant would happen? 191 00:12:11,360 --> 00:12:15,240 LY: It would be irresponsible for me to give you any number. 192 00:12:16,200 --> 00:12:18,320 CA: We're at TED. We're always irresponsible. 193 00:12:18,760 --> 00:12:20,496 LY: But we are working day and night 194 00:12:20,520 --> 00:12:22,600 trying to make this happen for the patients. 195 00:12:23,440 --> 00:12:26,336 CA: So not even, you won't say that you think it could happen 196 00:12:26,360 --> 00:12:28,736 within a decade or within five years or something? 197 00:12:28,760 --> 00:12:31,160 LY: For sure we hope it happens within one decade. 198 00:12:32,080 --> 00:12:34,016 (Laughter) 199 00:12:34,040 --> 00:12:37,656 CA: So there's a lot of people here who would be very, very excited at that, 200 00:12:37,680 --> 00:12:39,176 the potential is extraordinary. 201 00:12:39,200 --> 00:12:41,616 There will be some other people here who are going, 202 00:12:41,640 --> 00:12:42,896 "That pig is too cute. 203 00:12:42,920 --> 00:12:47,496 Humans shouldn't be exploiting something so cute for our benefit." 204 00:12:47,520 --> 00:12:49,960 Do you have any response to that? 205 00:12:51,120 --> 00:12:52,376 LY: Yeah, sure. 206 00:12:52,400 --> 00:12:57,296 So imagine one pig can save eight people's lives. 207 00:12:57,320 --> 00:13:00,416 In addition, similar to human donation, 208 00:13:00,440 --> 00:13:03,176 if we only harvest one kidney from the pig, 209 00:13:03,200 --> 00:13:05,096 the pig can still be alive, 210 00:13:05,120 --> 00:13:09,176 so we are very mindful about the issues, 211 00:13:09,200 --> 00:13:13,576 but I think our goal is just to address the unmet medical need 212 00:13:13,600 --> 00:13:16,296 for those patients and their families. 213 00:13:16,320 --> 00:13:19,600 CA: Plus, no one can say that to you if they eat bacon, right? 214 00:13:20,440 --> 00:13:21,656 LY: That's a good point. 215 00:13:21,680 --> 00:13:23,136 (Laughter) 216 00:13:23,160 --> 00:13:25,616 CA: Luhan, thank you so much. LY: Thank you so much. 217 00:13:25,640 --> 00:13:27,880 (Applause)