Richard Resnick: Welcome to the genomic revolution

225,288 views ・ 2011-09-15

TED


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翻译人员: Chunxiang Qian 校对人员: Felix Chen
女士们先生们,
00:16
Ladies and gentlemen,
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00:17
I present to you the human genome.
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我向您展示人类基因组
00:19
(Applause)
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(鼓掌)
00:23
Chromosome one -- top left, bottom right -- are the sex chromosomes.
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左上是一号染色体
右下是性染色体
00:27
Women have two copies of that big X chromosome;
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女性有两条那个大大的X染色体
男性有个X
00:30
men have the X and, of course, that small copy of the Y.
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当然,还有个小小的Y
00:33
Sorry boys, but it's just a tiny little thing that makes you different.
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男士们,不好意思,就是那个小东西让你不同
00:37
So if you zoom in on this genome,
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如果放大这条基因组
00:40
then what you see, of course, is this double-helix structure --
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你看到的当然就是这个双螺旋结构
00:43
the code of life spelled out with these four biochemical letters,
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生命的密码就是由这些生化的字母组成
或者说碱基,对吧:
00:46
or we call them bases: A, C, G and T.
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A, C, G 和 T
00:49
How many are there in the human genome? Three billion.
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人类基因组有多少这样的结构?30亿
00:51
Is that a big number?
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这个数字大吧?
00:53
Well, everybody can throw around big numbers.
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谁都能随便谈论大数字
00:55
But in fact, if I were to place one base
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但是,如果我把一个碱基放在
00:57
on each pixel of this 1280x800-resolution screen,
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这个1280×800屏幕的一个像素上
得要三千个屏幕一睹人类基因组
01:01
we would need 3,000 screens to take a look at the genome.
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所以这是非常大的
01:04
So it's really quite big.
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01:05
And perhaps because of its size,
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也许因为这个规模的缘故
01:07
a group of people -- all, by the way, with Y chromosomes --
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一群人-都是带Y染色体的
01:10
decided they would want to sequence it.
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他们决定进行测序
01:12
(Laughter)
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(笑声)
01:14
And so 15 years, actually, and about four billion dollars later,
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15年,实际上花了大约40亿
01:17
the genome was sequenced and published.
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基因组获得测序并公开了
01:19
In 2003, the final version was published, and they keep working on it.
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2003年最终“完成图”面世,他们继续完善它
这些都是由这样个机器完成的
01:23
That was all done on a machine like this.
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每个碱基大概要花费1美元
01:25
It costs about a dollar for each base -- a very slow way of doing it.
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这样工作非常缓慢
01:28
Well, folks, I'm here to tell you
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不过各位,我今天来要告诉你们
01:30
that the world has completely changed,
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这个世界大变模样了
01:32
and none of you know about it.
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你们还不知道呢
01:34
So now what we do is take a genome,
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我现在做的是获取一个基因组
01:36
we make maybe 50 copies of it,
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将其复制50份
01:38
we cut all those copies up into little 50-base reads,
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然后分割成50个碱基读数
01:41
and then we sequence them, massively parallel.
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然后进行大规模同时测序
01:43
Then we bring that into software and reassemble it,
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然后用软件
重新合成并给你解读
01:46
and tell you what the story is.
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为了让你更直观地了解
01:48
So to give you a picture of what this looks like,
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01:50
the Human Genome Project: 3 gigabases, right?
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人类基因组测序工程:3GB,
在这样的机器上测序:
01:53
One run on one of these modern machines: 200 gigabases in a week.
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一周可完成200GB
01:57
And that 200 is going to change to 600 this summer,
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这个夏天将有望提升至600
02:00
and there's no sign of this pace slowing.
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并且这种增长没有放缓的趋势
02:03
The price of a base, to sequence a base,
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所以每个碱基测序的价钱
02:06
has fallen 100 million times.
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下降了一千万倍
02:09
That's the equivalent of you filling up your car with gas in 1998,
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这就像你1998年给车加满油
等到2011年
02:13
waiting until 2011,
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02:14
and now you can drive to Jupiter and back twice.
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能到木星两个来回
02:16
(Laughter)
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(笑声)
02:21
World population,
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世界人口
PC配置
02:24
PC placements,
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02:25
the archive of all of medical literature,
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医学文献档案
02:28
Moore's law,
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摩尔定律
02:30
the old way of sequencing,
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旧的测序方式,然后是这些新玩意
02:32
and here's all the new stuff.
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各位,这是个对数尺度
02:34
Guys, this is a long scale;
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02:35
you don't typically see lines that go up like that.
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你不会常看到趋势像那样上升
02:38
So the worldwide capacity to sequence human genomes
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所以世界范围内可进行人类基因组测序的能力
今年大概是五万到十万人类基因组
02:42
is something like 50,000 to 100,000 human genomes this year.
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这是依据被配置的机器估算的
02:45
We know this based on the machines that are being placed.
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而这在未来可能会
02:48
This is expected to double, triple or maybe quadruple
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02:50
year over year for the foreseeable future.
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每年翻两番,三番,甚至四番
02:52
In fact, there's one lab in particular
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实际上,有一个实验室
02:54
that represents 20 percent of all that capacity:
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具备所有测序能力中的百分之二十
02:57
It's called the Beijing Genomics Institute.
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就是华大基因
03:00
The Chinese are absolutely winning this race to the new Moon, by the way.
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中国人毫无疑问正在领跑这场新的登月竞赛
03:04
What does this mean for medicine?
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这对药学来说什么意义呢?
03:06
So a woman, age 37,
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如果一个37岁的女性
她患有II期ER阳性乳腺癌
03:09
presents with stage 2 estrogen receptor-positive breast cancer.
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03:12
She is treated with surgery, chemotherapy and radiation.
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她正在接受手术治疗,化疗和放射治疗
03:15
She goes home.
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她回家了
03:17
Two years later,
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2年后,她发现患上III期C卵巢癌
03:18
she comes back with stage 3C ovarian cancer, unfortunately;
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不幸的是,再次接受手术和化疗
03:21
treated again with surgery and chemotherapy.
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03:23
She comes back three years later at age 42
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3年后她42岁
又患上卵巢癌,接受更多的化疗
03:26
with more ovarian cancer, more chemotherapy.
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03:28
Six months later,
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6个月后
03:30
she comes back with acute myeloid leukemia.
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她患上急性髓性白血病
03:34
She goes into respiratory failure and dies eight days later.
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最后呼吸衰竭八天后死亡
03:37
So first: the way in which this woman was treated,
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首先她接受的10年治疗
03:40
in as little as 10 years, will look like bloodletting.
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基本就是放血
03:43
And it's because of people like my colleague, Rick Wilson,
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正因为有人,比如我的同事,里克・威尔森
他工作与华盛顿大学的基因组研究所
03:46
at the Genome Institute at Washington University,
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03:48
who decided to take a look at this woman postmortem.
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决定对她尸检
他进行测序,他取了皮肤细胞,健康的皮肤
03:51
And he took skin cells, healthy skin
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03:53
and cancerous bone marrow,
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和癌化的骨髓
03:55
and sequenced the whole genomes of both of them
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他测定两者的所有基因组
区区几周后
03:58
in a couple of weeks, no big deal.
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04:00
Then he compared those two genomes in software,
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他用软件对比两组基因组
04:02
and what he found, among other things,
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他发现了
04:04
was a deletion -- a 2,000-base deletion across three billion bases
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30亿碱基里
有两千个碱基的丢失
04:08
in a particular gene called TP53.
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这是在一个叫TP53的基因上
如果这个基因发生有害突变
04:11
If you have this deleterious mutation in this gene,
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04:13
you're 90 percent likely to get cancer in your life.
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就有百分之九十的可能患癌
04:16
So unfortunately, this doesn't help this woman,
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很不幸这没能帮到这位女性
04:18
but it does have severe -- profound, if you will --
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但这对她的家人来说
04:21
implications to her family.
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是很重要深刻的启示
如果他们有同样的突变
04:24
I mean, if they have the same mutation,
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04:25
and they get this genetic test and they understand it,
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他们接受基因测试然后了解到该情况
04:28
then they can get regular screens and can catch cancer early,
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他们就可以接受常规检查并早点发现病症
04:31
and potentially live a significantly longer life.
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从而可以大大延长生命
04:33
Let me introduce you to the Beery twins,
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让我来介绍毕瑞兄妹
04:35
diagnosed with cerebral palsy at the age of two.
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他们在2岁时被诊断为脑瘫
他们的母亲是个非常勇敢的女性
04:38
Their mom is a very brave woman who didn't believe it;
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她不相信诊断符合症状
04:40
the symptoms weren't matching up.
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通过她不懈努力和网上搜索
04:42
And through some heroic efforts and a lot of Internet searching,
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她说服了医疗人员
04:45
she was able to convince the medical community
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他们患是另一种病
04:47
that, in fact, they had something else.
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多巴反应性肌张力失常
04:49
They had dopa-responsive dystonia.
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04:51
And so they were given L-Dopa,
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所以采用L-多巴治疗
04:53
and their symptoms did improve,
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他们的病情确实有所改善
04:55
but they weren't totally asymptomatic.
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但是并没有完全消除
04:57
Significant problems remained.
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仍然存在严重的问题
04:59
Turns out the gentleman in this picture is a guy named Joe Beery,
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照片中的男士叫乔・毕瑞
很幸运地他是
05:02
who was lucky enough to be the CIO
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一家叫做生命科技的公司的首席信息官
05:04
of a company called Life Technologies.
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这家公司是
05:06
They're one of two companies
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05:07
that makes these massive whole-genome sequencing tools.
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提供基因组测序设备的两大供应商之一
05:10
And so he got his kids sequenced.
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所以他测定他的孩子(的基因)
05:13
What they found was a series of mutations in a gene called SPR,
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他们发现了SPR基因上的一个系列突变
这个片段与产生血清素的功能相关
05:17
which is responsible for producing serotonin, among other things.
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05:20
So on top of L-Dopa, they gave these kids a serotonin precursor drug,
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所以除了L-多巴,他们也用血清素前体药物辅以治疗
05:23
and they're effectively normal now.
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孩子们恢复正常了
05:25
Guys, this would never have happened without whole-genome sequencing.
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各位,没有基因组测序这些都无法实现
当时,几年前的时候,花费高达10万美元
05:29
At the time -- this was a few years ago -- it cost $100,000.
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如今是一万美元,明年会是一千
05:31
Today it's $10,000, next year, $1,000,
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后年是一百
05:33
the year after, $100, give or take a year.
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就是这么快
05:35
That's how fast this is moving.
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这是小尼克
05:37
So here's little Nick --
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他喜欢蝙蝠侠和水枪
05:39
likes Batman and squirt guns.
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05:40
And it turns out Nick shows up at the children's hospital
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尼克去儿童医院接受治疗
05:44
with this distended belly, like a famine victim.
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他的肚子涨得像饥荒儿童一样
05:46
And it's not that he's not eating; it's that when he eats,
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这不是因为他不吃
而是他吃的时候,他的肠子就打开
05:49
his intestine basically opens up and feces spill out into his gut.
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废物进入腹腔
在经历了无数手术后
05:53
So a hundred surgeries later,
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05:54
he looks at his mom and says, "Mom, please pray for me.
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他看着妈妈说“妈妈,
为我祈祷吧,我十分痛苦“
05:58
I'm in so much pain."
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06:00
His pediatrician happens to have a background in clinical genetics
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他的儿科医生恰好有临床遗传学方面的背景
06:03
and he has no idea what's going on,
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他不知道问题出在哪儿
06:05
but he says, "Let's get this kid's genome sequenced."
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他说”让我们给他做基因组测序吧“
06:07
And what they find is a single-point mutation
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然后他们在控制程序性细胞死亡的基因上
06:09
in a gene responsible for controlling programmed cell death.
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发现一个单点突变
06:12
So the theory is that he's having some immunological reaction
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所以根源就是他对
06:15
to what's going on -- to the food, essentially.
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食物有种免疫反应
06:18
And that's a natural reaction, which causes some programmed cell death,
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这是种自然反应,它会导致程序性细胞死亡
06:21
but the gene that regulates that down is broken.
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但这个基因的此种功能出现问题
所以对于这个问题
06:24
And so this informs, among other things, of course,
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他接受了骨髓移植的治疗
06:26
a treatment for bone marrow transplant, which he undertakes.
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9个月艰难的康复期后
06:29
And after nine months of grueling recovery,
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他能吃A1沙司了
06:31
he's now eating steak with A1 sauce.
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(笑声)
06:33
(Laughter)
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06:34
The prospect of using the genome as a universal diagnostic
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利用基因组
作为万能诊断方法的前景
06:38
is upon us today.
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正在到来
就是今天,就在这里
06:41
Today. It's here.
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这对这屋子里的每一个人来说
06:43
And what it means for all of us
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06:44
is that everybody in this room could live an extra 5, 10, 20 years,
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意味着我们可以多活十到二十年
06:47
just because of this one thing.
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就是因为这项技术
06:49
Which is a fantastic story,
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这是个神奇的故事
06:51
unless you think about humanity's footprint on the planet,
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当然还有人类遍布全球的足迹
06:54
and our ability to keep up food production.
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和我们追赶粮食产量的能力
不过
06:57
So it turns out
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06:58
that the very same technology is also being used to grow new lines
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这项技术
同样可以被利用于
07:02
of corn, wheat, soybean and other crops
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种植新型玉米,麦子,大豆和其他粮食
07:05
that are highly tolerant of drought, of flood,
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能够抵抗干旱和洪水
07:07
of pests and pesticides.
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害虫和杀虫剂
07:09
Now, look --
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随着人口不断增长
07:11
as long as we continue to increase the population,
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我们会不得不使用转基因产品
07:13
we'll have to continue to grow and eat genetically modified foods.
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这是我的唯一立场
07:16
And that's the only position I'll take today.
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07:18
Unless there's anybody in the audience
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除非观众中有人
07:20
who'd like to volunteer to stop eating?
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决定绝食
不,没人会
07:23
None, not one.
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07:24
This is a typewriter,
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这是个打字机
07:26
a staple of every desktop for decades.
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数十年前每个书桌上都有一个
07:29
And, in fact, the typewriter was essentially deleted by this thing.
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实际上,打字机完全被这个取代了
07:33
And then more general versions of word processors came about.
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然后是更多代文字处理器面世
07:36
But ultimately, it was a disruption on top of a disruption.
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不过,最令人措手不及的
07:39
It was Bob Metcalfe inventing the Ethernet,
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还是鲍勃・梅得卡夫发明了以太网
07:41
and the connection of all these computers
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电脑的联网
07:43
that fundamentally changed everything.
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革命性地改变了一切
07:45
Suddenly we had Netscape, we had Yahoo.
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突然我们就有了Netscape,雅虎
07:48
And we had, indeed, the entire dot-com bubble.
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然后是整个互联网的泡沫经济
07:51
(Laughter)
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(笑声)
07:54
Not to worry though,
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不过别担心
07:56
that was quickly rescued by the iPod, Facebook
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iPod, Facebook又拯救了我们
07:58
and, indeed, Angry Birds.
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当然还有愤怒地小鸟
08:00
(Laughter)
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(笑声)
这就是我们今天所处(的环境)
08:03
Look, this is where we are today.
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08:05
This is the genomic revolution today. This is where we are.
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这是基因革命地时代,我们所处地时代
我希望你们考虑的是:
08:08
What I'd like you to consider is:
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如果这些点不是代表你的基因的碱基
08:10
What does it mean
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08:11
when these dots don't represent the individual bases of your genome,
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而是整个星球上基因相连
08:14
but they connect to genomes all across the planet?
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这意味着什么?
08:17
I just recently had to buy life insurance, and I was required to answer:
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我不久前才买了人身保险
我被这样问道:
08:21
A. I have never had a genetic test;
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A.我从来没有进行过基因测试,B.我有过,没戏了
08:23
B. I've had one, here you go;
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C.我有过但我不说出来
08:25
or C. I've had one and I'm not telling.
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很幸运,我还能选A
08:27
Thankfully, I was able to answer A,
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08:28
and I say that honestly, in case my life insurance agent is listening.
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要是我的保险代理人在听着的话我可确实没说谎
如果我选的是C呢?
08:32
But what would have happened if I had said C?
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08:34
Consumer applications for genomics will flourish.
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基因组学的消费需求将大大增加
你想不想知道
08:37
Do you want to see if you're genetically compatible
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你跟女友的基因是否兼容?当然
08:39
with your girlfriend?
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08:40
DNA sequencing on your iPhone? There's an app for that.
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要不要在你的iPhone上基因测序?有这么一个应用
08:43
(Laughter)
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(笑声)
08:45
Personalized genomic massage, anyone?
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有人想要个人定制的基因学按摩吗?
如今已经有个实验室
08:49
There's already a lab today that tests for allele 334 of the AVPR1 gene,
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为AVPR1基因上的等位基因334测序
所谓的欺骗基因
08:53
the so-called cheating gene.
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谁今天是和你重要的另一半一起来的
08:55
(Laughter)
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08:57
So anybody who's here today with your significant other,
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只要转过去,刮下他/她的口腔
08:59
just turn over to them, swab their mouth, send it to the lab
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寄到那个实验室你就知道了
09:02
and you'll know for sure.
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(笑声)
09:03
(Laughter)
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你想不想选一个
09:05
Do you really want to elect a president
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可能患心肌病的总统?
09:07
whose genome suggests cardiomyopathy?
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假设,现在是2016年
09:09
Think of it -- it's 2016,
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竞选人不仅公开
09:11
and the leading candidate releases
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她四年的税后申报
09:12
not only her four years of back-tax returns,
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还有她的个人基因组
09:15
but also her personal genome.
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看上去很不错
09:16
And it looks really good.
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09:17
Then she challenges all her competitors to do the same.
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然后她要求其他的竞争者也这么做
你觉得这不可能发生?
09:20
Do you think that's not going to happen?
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你觉得这会帮到约翰・麦凯恩?
09:22
Do you think it would have helped John McCain?
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(笑声)
09:24
(Laughter)
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观众里有多少人
09:26
How many people in the audience have the last name Resnick, like me?
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跟我同一个姓,雷斯尼克?请举手
09:29
Raise your hand.
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有人是吗? 没有
09:30
Anybody? Nobody.
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明显,有一两个
09:32
Typically, there's one or two.
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09:33
So my father's father was one of 10 Resnick brothers.
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我父亲是雷斯尼克10兄弟种的一个
他们相互不喜欢
09:36
They all hated each other, and all moved to different parts of the planet.
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他们移居到这世界上不同的角落
所以好比
09:40
So it's likely I'm related to every Resnick that I ever meet,
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我与我遇到过的雷斯尼克都有关系,但我不确定
09:43
but I don't know.
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09:44
So imagine if my genome were De-identified, sitting in software,
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试想如果我的基因组被确定,保存在软件里
09:47
And a third cousin's genome was also sitting there,
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一个三表兄弟的基因组也是
有软件可以对比两个(样本)
09:50
and there was software that could compare the two
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并且联系上
09:52
and make these associations.
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09:53
Not hard to imagine. My company has software that does this right now.
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不难想像,我的公司就有这样的软件
那么再像一下
09:57
Imagine one more thing,
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09:58
that that software is able to ask both parties for mutual consent:
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如果软件可向双方征询同意书
10:01
"Would you be willing to meet your third cousin?"
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“你想不想与你的三表兄见面?”
如果两人都说是
10:04
And if we both say yes -- voilà!
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10:05
Welcome to Chromosomally LinkedIn.
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耶!欢迎来到染色体LinkedIn网站
10:07
(Laughter)
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(笑声)
10:11
Now this is probably a good thing, right?
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这也许是个好事
10:13
Bigger clan gatherings and so on.
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你可以有个大家族
10:15
But maybe it's a bad thing as well.
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也可能是坏事
10:17
How many fathers in the room? Raise your hands.
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这屋子里有多少父亲?请举手
10:19
OK, so experts think that one to three percent of you
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好的,专家认为你们中间百分之一到三的人
10:22
are not actually the father of your child.
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并不是你孩子的父亲
10:24
(Laughter)
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(笑声)
10:26
Look --
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这个-
10:27
(Laughter)
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(笑声)
10:32
These genomes, these 23 chromosomes,
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这些基因组,这23个染色体
10:35
they don't in any way represent the quality of our relationships
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它们并不代表我们人际关系的质量
10:38
or the nature of our society -- at least not yet.
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或者我们这个社会的性质-至少目前还没有
如同任何新科技
10:41
And like any new technology,
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都取决与人类自己
10:43
it's really in humanity's hands
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10:44
to wield it for the betterment of mankind
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是否用于对人类有益的一面
10:47
or not.
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所以我强烈期望你们所有人醒悟
10:48
And so I urge you all to wake up and to tune in
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10:50
and to influence the genomic revolution that's happening all around you.
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并参与到这场发生在你们周围的基因革命
谢谢
10:54
Thank you.
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10:55
(Applause)
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(鼓掌)
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