How to create a world where no one dies waiting for a transplant | Luhan Yang

112,777 views ・ 2018-10-05

TED


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翻译人员: Ziyun Liao 校对人员: Yolanda Zhang
00:12
Hi everyone.
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大家好,
我想给大家介绍一下莱卡。
00:14
I would like to introduce you to Laika.
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00:17
To most of us, Laika is simply a very cute pig.
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对于大多数人来说, 莱卡只是一只非常可爱的猪,
00:22
However, to hundreds of thousands of patients in need of a lifesaving organ
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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,
00:29
Laika is a symbol of hope.
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莱卡则是希望的象征。
00:32
You see, ever since the 1970s,
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自1970年以来,
00:36
when organ transplants became a real option
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器官移植成为了一种现实的选择,
00:39
for patients with kidney failure and other organ diseases,
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对于肾脏衰竭以及其他患有 器官疾病的患者而言,
00:43
organ supply has been an issue.
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器官短缺一直都是个问题。
00:46
Over the last few decades,
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在过去的几十年,
00:48
the issue only worsened as organ demand has exponentially increased.
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这个问题日益严峻,因为 器官需求呈现了指数性增长。
00:55
Currently in the US,
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目前在美国,
00:57
there are close to 115,000 patients
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大概有11万5千名患者,
01:01
in need of a lifesaving organ transplant.
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需要器官移植才能继续活下去。
01:05
By the end of my talk,
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在我的演讲结束时,
01:07
one more patient will be added to this list.
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又会有一名新的病人加入到 器官移植的候选名单上。
01:12
Today, about 100 people will get a new organ,
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如今,大约有100个病人 会得到一个新鲜的器官,
01:16
a chance to start their life anew,
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一个重新开始新生活的机会,
01:19
and yet by the end of today,
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但是,在今天结束时,
01:22
20 others will die waiting.
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同样会有20人死于等待。
01:26
The situation is heartbreaking
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这样的情况令人心碎,
01:28
for patients, for their families
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无论是对病人,对他们的家人,
01:31
and for the doctors who want to do more.
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还是对于尽力挽救的 医生而言,都是如此。
01:36
In some parts of the world,
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在世界上的一些地方,
01:37
the situation also becomes a disturbing social issue.
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器官供应不足更成为了一种 令人忧心的社会问题,
01:42
In Asia, for example,
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比方说,在亚洲,
01:44
media outlets reported that desperate patients
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根据新闻媒体报道,许多绝望的病人
01:48
are obtaining organs from the cruel black market.
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残忍的在黑市购买新鲜的器官。
01:53
It is clear that a solution is needed to this crisis.
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很显然,这个问题亟待解决,
01:59
Human lives are at stake.
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因为人类的生存已经危若累卵。
02:03
As a biologist and a geneticist,
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作为一名生物学家和遗传学家,
02:06
it has become my mission to help solve this problem.
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我的使命就是想办法解决这个问题。
02:10
Today, I am optimistic to say that we are on our way there,
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今天,我可以很乐观的说, 我们已经正在朝向这个目标前进,
02:15
thanks to Laika.
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这一切全靠莱卡。
02:17
Using gene editing technology,
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基因编辑技术的使用,
02:19
it's now possible to exquisitely create a human-transplantable organ
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将精巧的创造人类 可移植器官变为了可能,
02:25
that can be safely grown in pigs.
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让这些器官能够 在猪身上安全的生长。
02:29
Before we jump into the incredible science that makes it happen,
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在我们沉浸于实现了这个 可能性的不可思议的技术前,
02:34
let's have a better understanding what xenotransplantation is.
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先好好了解一下什么是异种移植术。
02:39
It's a process of transplanting animal organs into humans.
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它是将动物的器官移植到 人类体内的一个过程。
02:44
You may want to ask, why pig organs?
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也许你会想问,为什么非得是猪的器官呢?
02:47
Because some pigs carry organs with similar size and physiology
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因为一些猪的器官与人类器官的
02:52
to human organs.
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大小和形态十分类似。
02:54
Over the last half a century,
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在过去的半个世纪,
02:56
pioneers of transplantation have tried hard to make it happen,
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器官移植的先驱们 在努力实现这一目标,
03:01
but with limited to no success.
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但基本上都以失败告终。
03:05
Why is that?
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为什么会这样呢?
03:06
Two fundamental hurdles stood in the way.
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因为存在两个难以跨越的障碍,
03:10
First is a problem of rejection.
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其一,就是排斥反应的问题。
03:13
When our immune system sees a new organ as foreign,
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当我们的免疫系统识别出异体器官时,
03:17
it will reject it.
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就会发生排斥反应。
03:19
Second, and this one is specific to the organs from the pig,
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其二,这种排斥反应 尤其针对猪的器官来源,
03:24
every pig carries a virus that is benign to the pig,
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每一只猪都携带着一种 对猪来说是良性的病毒,
03:29
but can be transmitted into humans.
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但这种病毒是可以传染到人类身上的,
03:31
It is called the porcine endogenous retrovirus (PERV),
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它被称为猪内源性逆转录病毒(PERV),
03:37
and this virus has the potential to cause a viral epidemic similar to HIV.
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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。
03:44
Without an effective way to address these issues,
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因为没有能有效解决这些问题的方法,
03:49
the field of xenotransplantation has been on hold for more than one decade.
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异种移植这个领域被搁置了十多年,
03:55
Little progress has been made, until now.
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期间几乎毫无进展。
04:01
Let me share with you how I got here today with Laika.
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我想跟大家分享一下我跟莱卡的故事。
04:06
My journey started from Emei Mountain in China.
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我的旅途始于中国峨眉山,
04:10
That is the place well described in a lot of legendary stories,
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这是一个被许多 传奇故事渲染过的地方,
04:14
like the "Crouching Tiger, Hidden Dragon."
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如《卧虎藏龙》,
04:17
That is the place I call home.
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那是一个我称为家的地方。
04:20
Growing up in the mountain,
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因为在这座山里长大,
04:22
I started to have a strong connection with nature.
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我与自然有了一种强烈的联系。
04:26
This is me when I was seven years old
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这是我七岁时候的样子,
04:29
standing in front of an ancient Buddhist temple
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站在一座古老的佛寺面前,
04:33
with a monkey on my shoulder.
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一只猴子站在我的肩上。
04:35
I still vividly remember how my friends and I
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我依然清楚的记得,我和朋友们
04:38
would toss peanuts around to distract the monkeys
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是如何在周围抛洒一些花生 来转移猴子们的注意力的,
04:42
so that we could cross to hike through the valley.
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这样才能开出一条路穿过那个村庄。
04:45
I love nature.
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我热爱自然,
04:47
When it was time to choose a field of study,
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到了选择研究领域的时候,
04:50
I chose to study biology at Peking University in Beijing.
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我选择了在北京大学学习生物。
04:55
However, the more I learned,
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然而,随着我学习的越多,
04:58
the more questions I had.
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我内心的疑问也越多。
05:00
How could our genetic makeup be so similar to animals
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人类的基因组成与动物是那么的类似,
05:05
and yet we look so different?
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但为何我们却看起来如此不同呢?
05:07
How is our immune system capable of fighting off so many pathogens
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我们的免疫系统是如何能够 在对抗入侵的病原体同时,
05:12
but smart enough not to attack ourselves.
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却又聪明到不会伤害自身?
05:16
Questions like this tormented me.
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这些问题一直折磨着我。
05:19
I know it sounds nerdy, but you know I'm a scientist.
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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。
05:24
After college, I decided I didn't want to just ask the questions,
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在大学毕业之后,我决定了, 我不要只是提出问题而已。
05:29
I wanted to answer them, so I did.
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我想要解决这些问题, 而我也确实这么做了。
05:33
In 2008, I was lucky enough to be accepted
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在2008年,我很幸运的收到了
05:37
into the PhD program at Harvard University
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来自哈佛大学博士项目的录取通知书,
05:41
and worked with Dr. George Church.
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能够和乔治 · 丘奇 (George Church)博士一起共事。
05:43
While working in Church's lab,
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在邱奇博士的实验室工作时,
05:45
I started to learn and experiment with the genetic makeup of mammals.
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我开始学习和使用 哺乳动物的基因组成进行实验。
05:51
Among all the experiments,
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在所有的这些实验中,
05:53
one particular one took me closer to Laika.
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其中一个特别的实验 让我向莱卡迈进了一步。
05:57
In 2013, my colleagues and I made changes in a human cell
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在2013年,我和同事们 成功修改了人类细胞,
06:03
using a tool you may have heard about
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使用的是也许各位已经听说过的,
06:05
called CRISPR.
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一种叫基因编辑的技术(CRISPR)。
06:07
We were one of the first two groups
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我们是首批实验成功的 两组里的其中一组,
06:10
to report the successful use of such a tool in changing our DNA.
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使用这项工具来编辑我们的DNA,
06:16
It was an exciting moment in scientific discovery.
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这是科学发现史上令人振奋的一刻。
06:20
The gene-editing tool CRISPR has two components.
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基因编辑工具CRISPR由两个部分组成,
06:25
It has a scissor called the enzyme CRISPR
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一个叫做酶CRISPR的剪刀,
06:28
and what is called a guide RNA.
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还有一个称为 向导RNA。
06:31
Think about it as genetic scissors with a microscope.
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我们可以把这套工具看作是 一个带有显微镜的遗传剪刀,
06:36
The microscope is a guide RNA,
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而这个显微镜就是 向导RNA,
06:39
which brings the scissors to the place we want to cut
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它将遗传剪刀带到我们想要剪切的部位,
06:43
and says, "Here it is,"
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告诉我们,“就是这儿了”,
06:45
and the enzyme CRISPR just cuts and repairs the DNA in the way we want.
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这样我们就能够准确地, 用酶CRISPR 对 DNA 进行剪切和修复。
06:51
Shortly after we reported our study,
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在我们报道了我们的研究后不久,
06:54
physicians at Mass General Hospital were intrigued by the medical applications
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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,
07:00
of our research.
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07:02
They reached out to us,
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于是他们联系了我们,
07:04
and together, we began to see the potential to use CRISPR
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然后我们就合作研究使用 CRISPR
07:08
to solve the organ shortage crisis.
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来解决器官供不应求的危机。
07:11
How do we do it?
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那么我们是怎么做的呢?
07:13
It is simple, yet very complex.
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说起来很简单,但实际操作很复杂。
07:18
We started by making changes in a pig's cell to make it virus-free
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我们首先编辑了猪的细胞, 让它不再携带病毒,
07:24
and human-immune-compatible.
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能够和人类免疫系统兼容。
07:26
The nucleus of that cell is then implanted into a pig egg
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再从脱毒了的细胞里提取细胞核, 植入到猪的卵细胞中,
07:31
and allowed to divide into an embryo.
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让其分裂成一个胚胎。
07:34
The resulting embryo is then placed into the uterus of a surrogate mother
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然后将形成的胚胎置于 代孕母猪的子宫中,
07:39
and allowed to divide into a pig.
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发育成一只完整的猪。
07:42
Basically, it's a process of cloning.
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说到底,其实就是克隆的过程。
07:45
The piglet then carries organs whose genetic makeup
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如果幸运的话, 那只小猪器官中的基因组成,
07:49
hopefully wouldn't be rejected by the human immune system.
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将不会受到人类免疫系统的排斥。
07:54
In 2015, our team decided to tackle the viral transmission problem first.
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2015年,我们的团队决定 先解决病毒传染的问题。
08:01
We wanted to take out all 62 copies of the PERV virus
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我们想要从猪的基因组中取出所有62份
08:07
from the pig genome,
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PERV 病毒的拷贝,
08:10
but at the time, it was nearly mission impossible.
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但在那个时候, 这基本上是不可能完成的任务。
08:14
Even with CRISPR,
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即使使用CRISPR,
08:15
we could only do one or two modifications within a cell.
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我们也只能在一个细胞内 对其中一或两处做出修改,
08:20
The record for number of modifications we can do in a particular cell was five.
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我们在一个特定的细胞内所做过 修改的最高记录是五处。
08:27
We had to increase the throughput by more than tenfold to achieve that.
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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。
08:33
With very careful design and hundreds of trials,
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经过仔细的设计和数百次实验,
08:37
we successfully took out all the virus,
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我们最终成功的取出了所有病毒,
08:40
broke the record.
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打破了基因修改的记录。
08:41
More importantly, our studies showed
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更重要的是,我们的研究表明,
08:44
that we could eliminate the possibility of this dangerous virus
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我们有可能消灭这些会被传播到
08:49
being transmitted into humans.
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人类身上的危险病毒。
08:53
Last year, with a modified cell and cloning technology,
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去年,凭借改良的细胞和克隆技术,
08:57
our startup, eGenesis, produced Laika,
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我们的公司,eGenesis, 成功培育了莱卡,
09:02
the first pig of its kind born without PERV.
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第一只相同品种,但天生 不携带PERV的猪。
09:07
(Applause)
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(掌声)
09:11
Laika represents the first critical step
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莱卡代表着在建立安全的
09:15
in establishing safe xenotransplantation.
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异种移植过程中第一个关键步骤。
09:19
It is also a platform
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同样,它也是我们
09:20
that we can do further genetic modification on
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对基因修改进行进一步研究的平台,
09:23
to solve the immunology problem.
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用以解决免疫学问题。
09:26
Since then, we have created more than 30 pigs without PERV,
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自那以后,我们又培育了 30多只不携带PERV的猪,
09:31
and they may be the most advanced geno-modified animal living on earth.
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它们也许是生活在地球上 最高级的转基因动物了。
09:38
We named Laika after the Soviet dog
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莱卡这个名字,取自苏联的一只狗,
09:41
who was the first animal to orbit the earth.
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它是第一只绕地球运行的动物。
09:45
We hope Laika and her siblings
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我们希望莱卡和它的兄弟姐妹们,
09:48
can lead us into a new frontier of science and medicine.
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可以带领我们走向 科学和医学的最前沿。
09:55
Imagine a world where patients who suffer from liver failure
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想象一下这样一个世界, 病人不再饱受肝脏衰竭的折磨,
10:00
can be saved with a new liver
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有新的肝脏帮助他们重获新生,
10:03
without having to wait for a donation
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他们再也不需要等待器官捐献,
10:06
or another human to die.
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或者另一个生命的陨落。
10:09
Imagine a world where people with diabetes
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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,
10:13
do not have to rely on insulin after every meal
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10:17
because we can provide them with good pancreatic cells
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因为我们能够给他们提供 健康的胰岛素细胞,
10:21
that can produce insulin on their own.
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能够自行产生胰岛素。
10:24
And imagine a world where patients with kidney failure
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再想象一个这样的世界, 患有肾衰竭的病人们,
10:29
do not have to face the burden of dialysis.
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不再需要面对透析 所带来的沉重负担。
10:34
We are striving to create that world,
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我们一直都在创造那样的世界,
10:38
a world without organ shortage.
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一个器官不再短缺的世界。
10:41
We finally have the tool to tackle the problem
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我们最终有了解决 器官供不应求的工具,
10:45
we could never tackle before,
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这是我们以前所办不到的,
10:47
and Laika is just the beginning of our journey.
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莱卡只是这漫漫征程中的第一步。
10:52
We have to be very humble in front of nature,
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在自然面前,我们必须得保持谦卑,
10:55
because there are more issues to be addressed,
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因为还有更多的问题需要解决,
10:58
including immunology
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包括免疫学,
10:59
and things we couldn't even anticipate at this point.
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以及我们此刻无法预料的一些事情。
11:04
However, it is our responsibility to translate the cutting-edge science
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然而,将最前沿的科学应用到医学中,
11:10
into medicine to save the lives of all the patients who are waiting.
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拯救那些还在等待器官移植的 病人的生命,我们义不容辞。
11:17
Thank you very much.
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谢谢大家。
11:18
(Applause)
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(掌声)
11:29
Chris Anderson: I mean, Luhan, this is extraordinary work here.
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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。
11:33
Come forward.
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来,我们向前走一点。
11:35
So what's the next steps here? You've got rid of the virus.
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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。
11:40
The next steps involve trying to get to the point
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下一步要做的是要试着解决
11:42
where a human body won't reject a transplant.
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让人类身体不会排斥 移植器官的问题吧。
11:46
What's involved in solving that?
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解决这个问题要涉及到什么呢?
11:49
Luhan Yang: It's a very complicated process.
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杨璐涵:这是一个非常复杂的过程。
11:51
So we need to take out the antigen of the pigs.
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我们需要取出猪的抗原。
11:55
In addition, we can learn a lot from cancer.
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此外,我们还可以从癌症上 学习到很多东西,
11:59
How can cancer invade or circumvent our immune system
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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,
12:03
so that we can utilize the trick of cancer
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我们就可以照葫芦画瓢,
12:08
and implement that on the pig organ
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运用在猪的器官上,
12:10
to fool our immune system to not attack the organ.
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让我们的免疫系统不去 攻击移植的器官。
12:15
CA: When would you estimate, when do you hope
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克里斯·安德森:你们预计 什么时候,或者你们希望
12:19
that the first successful transplant would happen?
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什么时候能首次实现 成功的异种移植呢?
12:23
LY: It would be irresponsible for me to give you any number.
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杨璐涵:我觉得现在就给出一个 数字是很不负责任的。
12:28
CA: We're at TED. We're always irresponsible.
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克里斯·安德森:没关系,在TED上 我们一向都是很不负责任的。
12:30
LY: But we are working day and night
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杨璐涵:但是我们已经夜以继日的
12:32
trying to make this happen for the patients.
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在为等待器官移植的病人 实现这个目标了。
12:35
CA: So not even, you won't say that you think it could happen
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克里斯·安德森: 所以你不认为,这件事
12:38
within a decade or within five years or something?
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在十年或五年内,又或者 什么时候能够发生吗?
12:40
LY: For sure we hope it happens within one decade.
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杨璐涵:我们当然希望能够 在十年内成功实现异种移植。
12:44
(Laughter)
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(笑声)
12:46
CA: So there's a lot of people here who would be very, very excited at that,
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克里斯·安德森:这里有很多人, 将会非常非常期待这一成功,
12:49
the potential is extraordinary.
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异种移植的潜力是巨大的。
但是同时也有这样的一些声音,
12:51
There will be some other people here who are going,
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“那些小猪那么可爱,
12:53
"That pig is too cute.
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12:54
Humans shouldn't be exploiting something so cute for our benefit."
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人类怎么可以因为一己私利 就去残害这些可爱的猪呢?”
12:59
Do you have any response to that?
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对此你会作何回应?
13:03
LY: Yeah, sure.
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杨璐涵:是的。
13:04
So imagine one pig can save eight people's lives.
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让我们想象一下, 一只猪就可以拯救八条人命。
13:09
In addition, similar to human donation,
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此外,跟人类器官捐献原理类似的是,
13:12
if we only harvest one kidney from the pig,
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如果我们一次只摘取猪一颗肾脏,
13:15
the pig can still be alive,
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那么这只猪将能够依然存活,
13:17
so we are very mindful about the issues,
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所以我们对这些问题十分关注。
13:21
but I think our goal is just to address the unmet medical need
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但是我想我们的目标只是为了解决 无法满足的医疗需求,
13:25
for those patients and their families.
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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。
13:28
CA: Plus, no one can say that to you if they eat bacon, right?
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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?
13:32
LY: That's a good point.
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杨璐涵:说的不错。
13:33
(Laughter)
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(笑声)
13:35
CA: Luhan, thank you so much. LY: Thank you so much.
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克里斯·安德森:璐涵,非常感谢你。 杨璐涵:谢谢你。
13:37
(Applause)
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(掌声)
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