Hi everyone. I would like to introduce you to Laika. To most of us, Laika is simply a very cute pig. However, to hundreds of thousands of patients in need of a lifesaving organ Laika is a symbol of hope. You see, ever since the 1970s, when organ transplants became a real option for patients with kidney failure and other organ diseases, organ supply has been an issue. Over the last few decades, the issue only worsened as organ demand has exponentially increased. Currently in the US, there are close to 115,000 patients in need of a lifesaving organ transplant. By the end of my talk, one more patient will be added to this list.
﻿大家好， 我想给大家介绍一下莱卡。 对于大多数人来说， 莱卡只是一只非常可爱的猪， 但是，对于成千上万个需要器官移植 来重获新生的患者而言， 莱卡则是希望的象征。 自1970年以来， 器官移植成为了一种现实的选择， 对于肾脏衰竭以及其他患有 器官疾病的患者而言， 器官短缺一直都是个问题。 在过去的几十年， 这个问题日益严峻，因为 器官需求呈现了指数性增长。 目前在美国， 大概有11万5千名患者， 需要器官移植才能继续活下去。 在我的演讲结束时， 又会有一名新的病人加入到 器官移植的候选名单上。
Today, about 100 people will get a new organ, a chance to start their life anew, and yet by the end of today, 20 others will die waiting. The situation is heartbreaking for patients, for their families and for the doctors who want to do more.
如今，大约有100个病人 会得到一个新鲜的器官， 一个重新开始新生活的机会， 但是，在今天结束时， 同样会有20人死于等待。 这样的情况令人心碎， 无论是对病人，对他们的家人， 还是对于尽力挽救的 医生而言，都是如此。
In some parts of the world, the situation also becomes a disturbing social issue. In Asia, for example, media outlets reported that desperate patients are obtaining organs from the cruel black market. It is clear that a solution is needed to this crisis. Human lives are at stake.
在世界上的一些地方， 器官供应不足更成为了一种 令人忧心的社会问题， 比方说，在亚洲， 根据新闻媒体报道，许多绝望的病人 残忍的在黑市购买新鲜的器官。 很显然，这个问题亟待解决， 因为人类的生存已经危若累卵。
As a biologist and a geneticist, it has become my mission to help solve this problem. Today, I am optimistic to say that we are on our way there, thanks to Laika. Using gene editing technology, it's now possible to exquisitely create a human-transplantable organ that can be safely grown in pigs.
作为一名生物学家和遗传学家， 我的使命就是想办法解决这个问题。 今天，我可以很乐观的说， 我们已经正在朝向这个目标前进， 这一切全靠莱卡。 基因编辑技术的使用， 将精巧的创造人类 可移植器官变为了可能， 让这些器官能够 在猪身上安全的生长。
Before we jump into the incredible science that makes it happen, let's have a better understanding what xenotransplantation is. It's a process of transplanting animal organs into humans. You may want to ask, why pig organs? Because some pigs carry organs with similar size and physiology to human organs.
在我们沉浸于实现了这个 可能性的不可思议的技术前， 先好好了解一下什么是异种移植术。 它是将动物的器官移植到 人类体内的一个过程。 也许你会想问，为什么非得是猪的器官呢？ 因为一些猪的器官与人类器官的 大小和形态十分类似。
Over the last half a century, pioneers of transplantation have tried hard to make it happen, but with limited to no success. Why is that? Two fundamental hurdles stood in the way. First is a problem of rejection. When our immune system sees a new organ as foreign, it will reject it. Second, and this one is specific to the organs from the pig, every pig carries a virus that is benign to the pig, but can be transmitted into humans. It is called the porcine endogenous retrovirus (PERV), and this virus has the potential to cause a viral epidemic similar to HIV. Without an effective way to address these issues, the field of xenotransplantation has been on hold for more than one decade. Little progress has been made, until now.
在过去的半个世纪， 器官移植的先驱们 在努力实现这一目标， 但基本上都以失败告终。 为什么会这样呢？ 因为存在两个难以跨越的障碍， 其一，就是排斥反应的问题。 当我们的免疫系统识别出异体器官时， 就会发生排斥反应。 其二，这种排斥反应 尤其针对猪的器官来源， 每一只猪都携带着一种 对猪来说是良性的病毒， 但这种病毒是可以传染到人类身上的， 它被称为猪内源性逆转录病毒（PERV）， 而这种病毒很有可能会产生 类似于HIV (艾滋病病毒) 的病毒性传染病。 因为没有能有效解决这些问题的方法， 异种移植这个领域被搁置了十多年， 期间几乎毫无进展。
Let me share with you how I got here today with Laika. My journey started from Emei Mountain in China. That is the place well described in a lot of legendary stories, like the "Crouching Tiger, Hidden Dragon." That is the place I call home. Growing up in the mountain, I started to have a strong connection with nature. This is me when I was seven years old standing in front of an ancient Buddhist temple with a monkey on my shoulder. I still vividly remember how my friends and I would toss peanuts around to distract the monkeys so that we could cross to hike through the valley.
我想跟大家分享一下我跟莱卡的故事。 我的旅途始于中国峨眉山， 这是一个被许多 传奇故事渲染过的地方， 如《卧虎藏龙》， 那是一个我称为家的地方。 因为在这座山里长大， 我与自然有了一种强烈的联系。 这是我七岁时候的样子， 站在一座古老的佛寺面前， 一只猴子站在我的肩上。 我依然清楚的记得，我和朋友们 是如何在周围抛洒一些花生 来转移猴子们的注意力的， 这样才能开出一条路穿过那个村庄。
I love nature. When it was time to choose a field of study, I chose to study biology at Peking University in Beijing. However, the more I learned, the more questions I had. How could our genetic makeup be so similar to animals and yet we look so different? How is our immune system capable of fighting off so many pathogens but smart enough not to attack ourselves. Questions like this tormented me. I know it sounds nerdy, but you know I'm a scientist.
我热爱自然， 到了选择研究领域的时候， 我选择了在北京大学学习生物。 然而，随着我学习的越多， 我内心的疑问也越多。 人类的基因组成与动物是那么的类似， 但为何我们却看起来如此不同呢？ 我们的免疫系统是如何能够 在对抗入侵的病原体同时， 却又聪明到不会伤害自身？ 这些问题一直折磨着我。 我知道这么说听起来很书呆子气， 但是你懂的，我是一名科学家。
After college, I decided I didn't want to just ask the questions, I wanted to answer them, so I did. In 2008, I was lucky enough to be accepted into the PhD program at Harvard University and worked with Dr. George Church. While working in Church's lab, I started to learn and experiment with the genetic makeup of mammals. Among all the experiments, one particular one took me closer to Laika. In 2013, my colleagues and I made changes in a human cell using a tool you may have heard about called CRISPR. We were one of the first two groups to report the successful use of such a tool in changing our DNA. It was an exciting moment in scientific discovery. The gene-editing tool CRISPR has two components. It has a scissor called the enzyme CRISPR and what is called a guide RNA. Think about it as genetic scissors with a microscope. The microscope is a guide RNA, which brings the scissors to the place we want to cut and says, "Here it is," and the enzyme CRISPR just cuts and repairs the DNA in the way we want.
在大学毕业之后，我决定了， 我不要只是提出问题而已。 我想要解决这些问题， 而我也确实这么做了。 在2008年，我很幸运的收到了 来自哈佛大学博士项目的录取通知书， 能够和乔治 · 丘奇 （George Church）博士一起共事。 在邱奇博士的实验室工作时， 我开始学习和使用 哺乳动物的基因组成进行实验。 在所有的这些实验中， 其中一个特别的实验 让我向莱卡迈进了一步。 在2013年，我和同事们 成功修改了人类细胞， 使用的是也许各位已经听说过的， 一种叫基因编辑的技术（CRISPR）。 我们是首批实验成功的 两组里的其中一组， 使用这项工具来编辑我们的DNA， 这是科学发现史上令人振奋的一刻。 基因编辑工具CRISPR由两个部分组成， 一个叫做酶CRISPR的剪刀， 还有一个称为 向导RNA。 我们可以把这套工具看作是 一个带有显微镜的遗传剪刀， 而这个显微镜就是 向导RNA， 它将遗传剪刀带到我们想要剪切的部位， 告诉我们，“就是这儿了”， 这样我们就能够准确地， 用酶CRISPR 对 DNA 进行剪切和修复。
Shortly after we reported our study, physicians at Mass General Hospital were intrigued by the medical applications of our research. They reached out to us, and together, we began to see the potential to use CRISPR to solve the organ shortage crisis. How do we do it? It is simple, yet very complex. We started by making changes in a pig's cell to make it virus-free and human-immune-compatible. The nucleus of that cell is then implanted into a pig egg and allowed to divide into an embryo. The resulting embryo is then placed into the uterus of a surrogate mother and allowed to divide into a pig. Basically, it's a process of cloning. The piglet then carries organs whose genetic makeup hopefully wouldn't be rejected by the human immune system. In 2015, our team decided to tackle the viral transmission problem first. We wanted to take out all 62 copies of the PERV virus from the pig genome, but at the time, it was nearly mission impossible. Even with CRISPR, we could only do one or two modifications within a cell. The record for number of modifications we can do in a particular cell was five. We had to increase the throughput by more than tenfold to achieve that. With very careful design and hundreds of trials, we successfully took out all the virus, broke the record. More importantly, our studies showed that we could eliminate the possibility of this dangerous virus being transmitted into humans.
在我们报道了我们的研究后不久， 几名麻省总医院的内科医生 对此项研究的医学应用前景深感兴趣， 于是他们联系了我们， 然后我们就合作研究使用 CRISPR 来解决器官供不应求的危机。 那么我们是怎么做的呢？ 说起来很简单，但实际操作很复杂。 我们首先编辑了猪的细胞， 让它不再携带病毒， 能够和人类免疫系统兼容。 再从脱毒了的细胞里提取细胞核， 植入到猪的卵细胞中，  让其分裂成一个胚胎。 然后将形成的胚胎置于 代孕母猪的子宫中， 发育成一只完整的猪。 说到底，其实就是克隆的过程。 如果幸运的话， 那只小猪器官中的基因组成， 将不会受到人类免疫系统的排斥。 2015年，我们的团队决定 先解决病毒传染的问题。 我们想要从猪的基因组中取出所有62份 PERV 病毒的拷贝， 但在那个时候， 这基本上是不可能完成的任务。 即使使用CRISPR， 我们也只能在一个细胞内 对其中一或两处做出修改， 我们在一个特定的细胞内所做过 修改的最高记录是五处。 想要达到取出所有病毒这个目标， 我们就得将数据提高十倍以上。 经过仔细的设计和数百次实验， 我们最终成功的取出了所有病毒， 打破了基因修改的记录。 更重要的是，我们的研究表明， 我们有可能消灭这些会被传播到 人类身上的危险病毒。
Last year, with a modified cell and cloning technology, our startup, eGenesis, produced Laika, the first pig of its kind born without PERV.
去年，凭借改良的细胞和克隆技术， 我们的公司，eGenesis， 成功培育了莱卡， 第一只相同品种，但天生 不携带PERV的猪。
(Applause)
（掌声）
Laika represents the first critical step in establishing safe xenotransplantation. It is also a platform that we can do further genetic modification on to solve the immunology problem. Since then, we have created more than 30 pigs without PERV, and they may be the most advanced geno-modified animal living on earth. We named Laika after the Soviet dog who was the first animal to orbit the earth. We hope Laika and her siblings can lead us into a new frontier of science and medicine.
莱卡代表着在建立安全的 异种移植过程中第一个关键步骤。 同样，它也是我们 对基因修改进行进一步研究的平台， 用以解决免疫学问题。 自那以后，我们又培育了 30多只不携带PERV的猪， 它们也许是生活在地球上 最高级的转基因动物了。 莱卡这个名字，取自苏联的一只狗， 它是第一只绕地球运行的动物。 我们希望莱卡和它的兄弟姐妹们， 可以带领我们走向 科学和医学的最前沿。
Imagine a world where patients who suffer from liver failure can be saved with a new liver without having to wait for a donation or another human to die. Imagine a world where people with diabetes do not have to rely on insulin after every meal because we can provide them with good pancreatic cells that can produce insulin on their own. And imagine a world where patients with kidney failure do not have to face the burden of dialysis. We are striving to create that world, a world without organ shortage. We finally have the tool to tackle the problem we could never tackle before, and Laika is just the beginning of our journey. We have to be very humble in front of nature, because there are more issues to be addressed, including immunology and things we couldn't even anticipate at this point. However, it is our responsibility to translate the cutting-edge science into medicine to save the lives of all the patients who are waiting.
想象一下这样一个世界， 病人不再饱受肝脏衰竭的折磨， 有新的肝脏帮助他们重获新生， 他们再也不需要等待器官捐献， 或者另一个生命的陨落。 想象一个这样的世界， 糖尿病人们不再需要在 饭后摄入胰岛素， 因为我们能够给他们提供 健康的胰岛素细胞， 能够自行产生胰岛素。 再想象一个这样的世界， 患有肾衰竭的病人们， 不再需要面对透析 所带来的沉重负担。 我们一直都在创造那样的世界， 一个器官不再短缺的世界。 我们最终有了解决 器官供不应求的工具， 这是我们以前所办不到的， 莱卡只是这漫漫征程中的第一步。 在自然面前，我们必须得保持谦卑， 因为还有更多的问题需要解决， 包括免疫学， 以及我们此刻无法预料的一些事情。 然而，将最前沿的科学应用到医学中， 拯救那些还在等待器官移植的 病人的生命，我们义不容辞。
Thank you very much.
谢谢大家。
(Applause)
（掌声）
Chris Anderson: I mean, Luhan, this is extraordinary work here. Come forward. So what's the next steps here? You've got rid of the virus. The next steps involve trying to get to the point where a human body won't reject a transplant. What's involved in solving that?
克里斯·安德森：璐涵，我想说， 你们走到这一步已经非常了不起了。 来，我们向前走一点。 那么你们的下一步工作是什么呢？ 你们现在已经去除了病毒了。 下一步要做的是要试着解决 让人类身体不会排斥 移植器官的问题吧。 解决这个问题要涉及到什么呢？
Luhan Yang: It's a very complicated process. So we need to take out the antigen of the pigs. In addition, we can learn a lot from cancer. How can cancer invade or circumvent our immune system so that we can utilize the trick of cancer and implement that on the pig organ to fool our immune system to not attack the organ.
杨璐涵：这是一个非常复杂的过程。 我们需要取出猪的抗原。 此外，我们还可以从癌症上 学习到很多东西， 比如通过研究癌细胞是如何 入侵或绕过我们的免疫系统的小技巧， 我们就可以照葫芦画瓢， 运用在猪的器官上， 让我们的免疫系统不去 攻击移植的器官。
CA: When would you estimate, when do you hope that the first successful transplant would happen?
克里斯·安德森：你们预计 什么时候，或者你们希望 什么时候能首次实现 成功的异种移植呢？
LY: It would be irresponsible for me to give you any number.
杨璐涵：我觉得现在就给出一个 数字是很不负责任的。
CA: We're at TED. We're always irresponsible.
克里斯·安德森：没关系，在TED上 我们一向都是很不负责任的。
LY: But we are working day and night trying to make this happen for the patients.
杨璐涵：但是我们已经夜以继日的 在为等待器官移植的病人 实现这个目标了。
CA: So not even, you won't say that you think it could happen within a decade or within five years or something?
克里斯·安德森： 所以你不认为，这件事 在十年或五年内，又或者 什么时候能够发生吗？
LY: For sure we hope it happens within one decade.
杨璐涵：我们当然希望能够 在十年内成功实现异种移植。
(Laughter)
（笑声）
CA: So there's a lot of people here who would be very, very excited at that, the potential is extraordinary. There will be some other people here who are going, "That pig is too cute. Humans shouldn't be exploiting something so cute for our benefit." Do you have any response to that?
克里斯·安德森：这里有很多人， 将会非常非常期待这一成功， 异种移植的潜力是巨大的。 但是同时也有这样的一些声音， “那些小猪那么可爱， 人类怎么可以因为一己私利 就去残害这些可爱的猪呢？” 对此你会作何回应？
LY: Yeah, sure. So imagine one pig can save eight people's lives. In addition, similar to human donation, if we only harvest one kidney from the pig, the pig can still be alive, so we are very mindful about the issues, but I think our goal is just to address the unmet medical need for those patients and their families.
杨璐涵：是的。 让我们想象一下， 一只猪就可以拯救八条人命。 此外，跟人类器官捐献原理类似的是， 如果我们一次只摘取猪一颗肾脏， 那么这只猪将能够依然存活， 所以我们对这些问题十分关注。 但是我想我们的目标只是为了解决 无法满足的医疗需求，  为了那些需要等待器官移植的病人， 以及让他们的家人不再痛苦。
CA: Plus, no one can say that to you if they eat bacon, right?
克里斯·安德森：还有就是，那些吃 培根的人也没有资格指责你们，对吗？
LY: That's a good point.
杨璐涵：说的不错。
(Laughter) CA: Luhan, thank you so much. LY: Thank you so much. (Applause)
（笑声） 克里斯·安德森：璐涵，非常感谢你。 杨璐涵：谢谢你。 （掌声）