1 00:00:01,163 --> 00:00:02,291 Hi everyone. 2 00:00:02,291 --> 00:00:05,932 I would like to introduce you to Laika. 3 00:00:05,932 --> 00:00:10,825 To most of us, Laika is simply a very cute pig. 4 00:00:10,825 --> 00:00:17,182 However, to hundreds of thousands of patients in need of a lifesaving organ, 5 00:00:17,182 --> 00:00:20,061 Laika is a symbol of hope. 6 00:00:21,160 --> 00:00:24,264 You see, ever since the 1970s, 7 00:00:24,264 --> 00:00:27,654 when organ transplants became a real option 8 00:00:27,654 --> 00:00:31,844 for patients with kidney failure and other organ diseases, 9 00:00:31,844 --> 00:00:35,022 organ supply has been an issue. 10 00:00:35,022 --> 00:00:36,979 Over the last few decades, 11 00:00:36,979 --> 00:00:42,306 the issue only worsened as organ demand has exponentially increased. 12 00:00:43,141 --> 00:00:45,725 Currently in the US, 13 00:00:45,725 --> 00:00:50,024 there are close to 115,000 patients 14 00:00:50,024 --> 00:00:53,738 in need of a lifesaving organ transplant. 15 00:00:53,738 --> 00:00:55,580 By the end of my talk, 16 00:00:55,580 --> 00:01:00,337 one more patient will be added to this list. 17 00:01:00,337 --> 00:01:04,575 Today, about 100 people will get a new organ, 18 00:01:04,575 --> 00:01:08,423 a chance to start their life anew, 19 00:01:08,423 --> 00:01:10,695 and yet by the end of today, 20 00:01:10,695 --> 00:01:13,703 20 others will die waiting. 21 00:01:14,462 --> 00:01:16,730 The situation is heartbreaking 22 00:01:16,730 --> 00:01:19,939 for patients, for their families, 23 00:01:19,939 --> 00:01:23,518 and for the doctors who want to do more. 24 00:01:24,293 --> 00:01:26,187 In some parts of the world, 25 00:01:26,187 --> 00:01:30,510 the situation also becomes a disturbing social issue. 26 00:01:30,510 --> 00:01:32,309 In Asia, for example, 27 00:01:32,309 --> 00:01:36,485 media outlets reported that desperate patients 28 00:01:36,485 --> 00:01:38,741 are obtaining organs 29 00:01:38,741 --> 00:01:41,862 from the cruel black market. 30 00:01:41,862 --> 00:01:47,373 It is clear that a solution is needed to this crisis. 31 00:01:47,373 --> 00:01:50,433 Human lives are at stake. 32 00:01:51,417 --> 00:01:54,466 As a biologist and a geneticist, 33 00:01:54,466 --> 00:01:58,453 it has become my mission to help solve this problem. 34 00:01:58,987 --> 00:02:04,070 Today, I am optimistic to say that we are on our way there, 35 00:02:04,070 --> 00:02:05,845 thanks to Laika. 36 00:02:05,845 --> 00:02:08,192 Using gene editing technology, 37 00:02:08,192 --> 00:02:14,006 it's now possible to exclusively create a human transplantable organ 38 00:02:14,006 --> 00:02:16,928 that can be safely grown in pigs. 39 00:02:18,135 --> 00:02:22,437 Before we jump into the incredible science that makes it happen, 40 00:02:22,437 --> 00:02:27,128 let's have a better understanding what xenotransplantation is. 41 00:02:27,441 --> 00:02:32,252 It's a process of transplanting animal organs into humans. 42 00:02:32,252 --> 00:02:35,785 You may want to ask, why pig organs? 43 00:02:35,785 --> 00:02:40,612 Because some pigs carry organs with similar size and physiology 44 00:02:40,612 --> 00:02:42,471 to human organs. 45 00:02:42,471 --> 00:02:45,027 Over the last half a century, 46 00:02:45,027 --> 00:02:49,855 pioneers of transplantation have tried hard to make it happen, 47 00:02:49,855 --> 00:02:53,250 but with limited to no success. 48 00:02:53,472 --> 00:02:54,906 Why is that? 49 00:02:54,906 --> 00:02:58,515 Two fundamental hurdles stood in the way. 50 00:02:58,515 --> 00:03:01,695 First is a problem of rejection. 51 00:03:01,695 --> 00:03:05,558 When our immune system sees a new organ as foreign, 52 00:03:05,558 --> 00:03:07,754 it will reject it. 53 00:03:07,754 --> 00:03:12,322 Second, and this one is specific to the organs from the pig, 54 00:03:12,322 --> 00:03:17,502 every pig carries a virus that has been ?? to the pig, 55 00:03:17,502 --> 00:03:20,157 but can be transmitted into humans. 56 00:03:20,157 --> 00:03:24,569 It is called the porcine endogenous retrovirus (PERV), 57 00:03:24,569 --> 00:03:30,160 and this virus has the potential to cause a viral epidemic 58 00:03:30,160 --> 00:03:32,647 similar to HIV. 59 00:03:32,647 --> 00:03:37,098 Without an effective way to address these issues, 60 00:03:37,098 --> 00:03:43,909 the field of xenotransplantation has been on hold for more than one decade. 61 00:03:43,909 --> 00:03:48,383 Little progress has been made, until now. 62 00:03:49,719 --> 00:03:54,160 Let me share with you how I got here today with Laika. 63 00:03:54,538 --> 00:03:58,638 My journey started from ?? Mountain in China. 64 00:03:58,638 --> 00:04:03,031 That is the place ?? described in a lot of legendary stories, 65 00:04:03,031 --> 00:04:06,088 like the "Crouching Tiger, Hidden Dragon." 66 00:04:06,088 --> 00:04:09,208 That is the place I call home. 67 00:04:09,208 --> 00:04:10,935 Growing up in the mountain, 68 00:04:10,935 --> 00:04:14,967 I started to have a strong connection with nature. 69 00:04:14,967 --> 00:04:18,033 This is me when I was seven years old 70 00:04:18,033 --> 00:04:21,529 standing in front of an ancient Buddhist temple 71 00:04:21,529 --> 00:04:23,554 with a monkey on my shoulder. 72 00:04:23,554 --> 00:04:26,997 I still vividly remember how my friends and I 73 00:04:26,997 --> 00:04:30,263 would toss the peanuts around to distract the monkeys 74 00:04:30,263 --> 00:04:33,641 so that we could cross to hike through the valley. 75 00:04:34,024 --> 00:04:35,605 I loved nature. 76 00:04:35,605 --> 00:04:38,457 When it was time to choose a field of study, 77 00:04:38,457 --> 00:04:44,002 I chose to study biology at Peking University in Beijing. 78 00:04:44,002 --> 00:04:46,522 However, the more I learned, 79 00:04:46,522 --> 00:04:48,805 the more questions I had. 80 00:04:48,805 --> 00:04:53,314 How could our genetic makeup be so similar to animals, 81 00:04:53,314 --> 00:04:56,252 and yet we look so different? 82 00:04:56,252 --> 00:05:00,871 How is our immune system capable of fighting off so many pathogens 83 00:05:00,871 --> 00:05:04,403 but smart enough not to attack ourselves. 84 00:05:04,596 --> 00:05:08,186 Questions like this tormented me. 85 00:05:08,186 --> 00:05:12,187 I know it sounds nerdy, but you know I'm a scientist. 86 00:05:12,187 --> 00:05:17,471 After college, I decided I didn't want to just ask the questions, 87 00:05:17,471 --> 00:05:21,888 I wanted to answer them, so I did. 88 00:05:21,888 --> 00:05:29,404 In 2008, I was lucky enough to be accepted into the PhD program at Harvard University 89 00:05:29,404 --> 00:05:31,940 and worked with Dr. George Church. 90 00:05:32,222 --> 00:05:36,643 While working in Church's lab, I started to learn and experiment with 91 00:05:36,643 --> 00:05:39,514 the genetic makeup of mammals. 92 00:05:39,514 --> 00:05:42,169 Among all the experiments, 93 00:05:42,169 --> 00:05:45,800 one particular one took me closer to Laika. 94 00:05:45,800 --> 00:05:51,728 In 2013, my colleagues and I made changes in a human cell 95 00:05:51,728 --> 00:05:54,861 using a tool you may have heard about 96 00:05:54,861 --> 00:05:56,116 called CRISPR. 97 00:05:56,116 --> 00:05:59,608 We were one of the first two groups 98 00:05:59,608 --> 00:06:04,483 to report the successful use of such a tool in changing our DNA. 99 00:06:04,483 --> 00:06:09,066 It was an exciting moment in scientific discovery. 100 00:06:09,066 --> 00:06:13,545 The gene-editing tool CRISPR has two components. 101 00:06:13,545 --> 00:06:16,775 It has a scissor called the ??, 102 00:06:16,775 --> 00:06:20,251 and what is called a guide RNA. 103 00:06:20,251 --> 00:06:24,376 Think about it as a genetic scissors with a microscope. 104 00:06:24,376 --> 00:06:27,661 The microscope is a guide RNA, 105 00:06:27,661 --> 00:06:31,539 which brings the scissors to the place we want to cut 106 00:06:31,539 --> 00:06:33,494 and says, "Here it is," 107 00:06:33,494 --> 00:06:38,910 and the ?? CRISPR just cuts and repairs the DNA in the way we want. 108 00:06:39,951 --> 00:06:43,197 Shortly after we reported our study, 109 00:06:43,197 --> 00:06:49,025 physicians at Mass General Hospital were intrigued by the medical applications 110 00:06:49,025 --> 00:06:50,764 of our research. 111 00:06:50,764 --> 00:06:54,130 They reached out to us, 112 00:06:54,130 --> 00:06:56,401 and together, we began to see the potential to use CRISPR 113 00:06:56,401 --> 00:07:00,227 to solve the organ shortage crisis. 114 00:07:00,227 --> 00:07:01,835 How do we do it? 115 00:07:01,835 --> 00:07:06,297 It is simple, yet very complex. 116 00:07:06,297 --> 00:07:11,349 We started by making changes in a pig's cell to make virus-free 117 00:07:11,349 --> 00:07:15,273 and human-immune-compatible. 118 00:07:15,273 --> 00:07:19,918 The nucleus of that cell is then implanted into a pig egg 119 00:07:19,918 --> 00:07:22,944 and allowed to divide into an embryo. 120 00:07:22,944 --> 00:07:28,484 The resulting embryo is then placed into the uterus of a surrogate mother 121 00:07:28,484 --> 00:07:31,070 and allowed to divide into a pig. 122 00:07:31,070 --> 00:07:34,030 Basically, it's a process of cloning. 123 00:07:34,030 --> 00:07:37,947 The piglet then carries organs whose genetic makeup 124 00:07:37,947 --> 00:07:41,266 hopefully wouldn't be rejected by the human immune system. 125 00:07:42,914 --> 00:07:49,711 In 2015, our team decided to tackle the viral transmission problem first. 126 00:07:49,711 --> 00:07:58,330 We wanted to take out all 62 copies of the PERV virus from the pig genome, 127 00:07:58,330 --> 00:08:02,495 but at the time, it was nearly mission impossible. 128 00:08:02,495 --> 00:08:05,348 Even with CRISPR, 129 00:08:05,348 --> 00:08:08,938 we could only do one or two modifications within a cell. 130 00:08:08,938 --> 00:08:15,475 The record for number of modifications we can do in a particular cell was five. 131 00:08:15,475 --> 00:08:21,382 We had to increase the through-put by more than tenfold to achieve that. 132 00:08:21,382 --> 00:08:25,354 With very careful design and hundreds of trials, 133 00:08:25,354 --> 00:08:29,313 we successfully took out all the virus, 134 00:08:29,313 --> 00:08:30,589 broke the record. 135 00:08:30,589 --> 00:08:34,714 More importantly, our studies showed that we could eliminate 136 00:08:34,714 --> 00:08:37,773 the possibility of this dangerous virus 137 00:08:37,773 --> 00:08:40,547 being transmitted into humans. 138 00:08:41,346 --> 00:08:45,706 Last year, with a modified cell and cloning technology, 139 00:08:45,706 --> 00:08:50,478 our startup, eGenesis, produced Laika, 140 00:08:50,478 --> 00:08:55,496 the first pig of its kind born without PERV. 141 00:08:55,496 --> 00:08:59,520 (Applause) 142 00:08:59,709 --> 00:09:07,276 Laika represents the first critical step in establishing safe xenotransplantation. 143 00:09:07,276 --> 00:09:09,529 It is also a platform 144 00:09:09,529 --> 00:09:12,251 that we can do further genetic modification on 145 00:09:12,251 --> 00:09:15,169 to solve the immunology problem. 146 00:09:15,169 --> 00:09:20,208 Since then, we have created more than 30 pigs without PERV, 147 00:09:20,208 --> 00:09:26,295 and they may be the most advanced geno-modified animal living on Earth. 148 00:09:26,295 --> 00:09:29,762 We named Laika after the Soviet dog 149 00:09:29,762 --> 00:09:33,620 who was the first animal to orbit the Earth. 150 00:09:33,620 --> 00:09:36,812 We hope Laika and her siblings 151 00:09:36,812 --> 00:09:43,694 can lead us into a new frontier of science and medicine. 152 00:09:43,694 --> 00:09:48,801 Imagine a world where patients who suffer from liver failure 153 00:09:48,801 --> 00:09:51,739 can be saved with a new liver 154 00:09:51,739 --> 00:09:54,923 without having to wait for a donation 155 00:09:54,923 --> 00:09:57,848 or another human to die. 156 00:09:57,848 --> 00:10:01,917 Imagine a world where people with diabetes 157 00:10:01,917 --> 00:10:05,775 do not have to rely on insulin after every meal 158 00:10:05,775 --> 00:10:09,956 because we can provide them with good pancreatic cells 159 00:10:09,956 --> 00:10:12,927 that can produce insulin on their own. 160 00:10:12,927 --> 00:10:17,841 And imagine a world where patients with kidney failure 161 00:10:17,841 --> 00:10:22,773 do not have the face the burden of dialysis. 162 00:10:22,773 --> 00:10:26,394 We are striving to create that world, 163 00:10:26,394 --> 00:10:29,994 a world without organ shortage. 164 00:10:29,994 --> 00:10:34,410 We finally have the tool to tackle the problem 165 00:10:34,410 --> 00:10:36,083 we could never tackle before, 166 00:10:36,083 --> 00:10:40,132 and Laika is just the beginning of our journey. 167 00:10:40,132 --> 00:10:43,881 We have to be very humble in front of nature, 168 00:10:43,881 --> 00:10:46,560 because there are more issues to be addressed, 169 00:10:46,560 --> 00:10:48,390 including immunology 170 00:10:48,390 --> 00:10:53,116 and things we couldn't even anticipate at this point. 171 00:10:53,116 --> 00:10:59,179 However, it is our responsibility to translate the cutting edge science 172 00:10:59,179 --> 00:11:00,598 into medicine to save the lives of all the patients who are waiting. 173 00:11:00,598 --> 00:11:07,029 Thank you very much. 174 00:11:07,029 --> 00:11:09,121 (Applause) 175 00:11:15,994 --> 00:11:21,901 Chris Anderson: I mean, Luhan, this is extraordinary work here. 176 00:11:21,901 --> 00:11:23,956 Come forward. 177 00:11:23,956 --> 00:11:28,427 So what's the next steps here? You've got rid of the virus. 178 00:11:28,427 --> 00:11:31,280 The next steps involve trying to get to the point 179 00:11:31,280 --> 00:11:34,504 where a human body won't reject a transplant. 180 00:11:34,504 --> 00:11:36,402 What's involved in solving that? 181 00:11:36,402 --> 00:11:39,664 Luhan Yang: It's a very complicated process. 182 00:11:39,664 --> 00:11:44,210 So we need to take out the ?? of the pigs. 183 00:11:44,210 --> 00:11:47,684 In addition, we can learn a lot from cancer. 184 00:11:47,684 --> 00:11:51,793 How can cancer invade or circumvent our immune system 185 00:11:51,793 --> 00:11:55,606 so that we can utilize the trick of cancer 186 00:11:55,606 --> 00:11:58,999 and implement that on the pig organ 187 00:11:58,999 --> 00:12:03,463 to fool our immune system to not attack the organ. 188 00:12:03,463 --> 00:12:07,425 CA: When would you estimate, when do you hope, 189 00:12:07,425 --> 00:12:11,480 that the first successful transplant would happen? 190 00:12:11,480 --> 00:12:15,336 LY: It would be irresponsible for me to give you any number. 191 00:12:15,336 --> 00:12:19,025 CA: We're at TED. We're always irresponsible. 192 00:12:19,025 --> 00:12:22,165 LY: But we are working day and night trying to make this happen 193 00:12:22,165 --> 00:12:23,716 for the patients. 194 00:12:23,716 --> 00:12:27,281 CA: So not even, you won't say that you think it could happen 195 00:12:27,281 --> 00:12:29,607 within a decade or within five years or something? 196 00:12:29,607 --> 00:12:32,311 LY: For sure we hope it happens within one decade. 197 00:12:32,311 --> 00:12:34,186 (Laughter) 198 00:12:34,186 --> 00:12:38,548 CA: So there's a lot of people here who would be very, very excited at that, 199 00:12:38,548 --> 00:12:39,397 and the potential is extraordinary. 200 00:12:39,397 --> 00:12:40,995 There will be some other people here who are going, 201 00:12:40,995 --> 00:12:43,245 "That pig is too cute. 202 00:12:43,245 --> 00:12:47,830 Humans shouldn't be exploiting something so cute for our benefit." 203 00:12:47,830 --> 00:12:51,446 Do you have any response to that? 204 00:12:51,446 --> 00:12:55,524 LY: Yeah, sure. 205 00:12:55,524 --> 00:12:57,696 So imagine one pig can save eight people's lives. 206 00:12:57,696 --> 00:13:01,144 In addition, similar to human donation, 207 00:13:01,144 --> 00:13:03,464 if we only harvest one kidney from the pig, 208 00:13:03,464 --> 00:13:05,493 the pig can still be alive, 209 00:13:05,493 --> 00:13:09,572 so we are very mindful about the issues, 210 00:13:09,572 --> 00:13:13,937 but I think our goal is just to address the unmet medical need 211 00:13:13,937 --> 00:13:16,883 for those patients and their families. 212 00:13:16,883 --> 00:13:20,344 CA: Plus, no one can say that to you if they eat bacon, right? 213 00:13:20,344 --> 00:13:22,714 LY: That's a good point. 214 00:13:22,714 --> 00:13:23,950 (Laughter) 215 00:13:23,950 --> 00:13:26,212 CA: Luhan, thank you so much. LY: Thank you so much. 216 00:13:26,212 --> 00:13:27,892 (Applause)