Richard Resnick: Welcome to the genomic revolution

翻译人员: Chunxiang Qian 校对人员: Felix Chen

女士们先生们，

Ladies and gentlemen,

I present to you the human genome.

我向您展示人类基因组

(Applause)

（鼓掌）

Chromosome one -- top left, bottom right -- are the sex chromosomes.

左上是一号染色体

右下是性染色体

Women have two copies of that big X chromosome;

女性有两条那个大大的X染色体

男性有个X

men have the X and, of course, that small copy of the Y.

当然，还有个小小的Y

Sorry boys, but it's just a tiny little thing that makes you different.

男士们，不好意思，就是那个小东西让你不同

So if you zoom in on this genome,

如果放大这条基因组

then what you see, of course, is this double-helix structure --

你看到的当然就是这个双螺旋结构

the code of life spelled out with these four biochemical letters,

生命的密码就是由这些生化的字母组成

或者说碱基，对吧：

or we call them bases: A, C, G and T.

A, C, G 和 T

How many are there in the human genome? Three billion.

人类基因组有多少这样的结构？30亿

Is that a big number?

这个数字大吧？

Well, everybody can throw around big numbers.

谁都能随便谈论大数字

But in fact, if I were to place one base

但是，如果我把一个碱基放在

on each pixel of this 1280x800-resolution screen,

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

we would need 3,000 screens to take a look at the genome.

所以这是非常大的

So it's really quite big.

And perhaps because of its size,

也许因为这个规模的缘故

a group of people -- all, by the way, with Y chromosomes --

一群人－都是带Y染色体的

decided they would want to sequence it.

他们决定进行测序

(Laughter)

（笑声）

And so 15 years, actually, and about four billion dollars later,

15年，实际上花了大约40亿

the genome was sequenced and published.

基因组获得测序并公开了

In 2003, the final version was published, and they keep working on it.

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

That was all done on a machine like this.

每个碱基大概要花费1美元

It costs about a dollar for each base -- a very slow way of doing it.

这样工作非常缓慢

Well, folks, I'm here to tell you

不过各位，我今天来要告诉你们

that the world has completely changed,

这个世界大变模样了

and none of you know about it.

你们还不知道呢

So now what we do is take a genome,

我现在做的是获取一个基因组

we make maybe 50 copies of it,

将其复制50份

we cut all those copies up into little 50-base reads,

然后分割成50个碱基读数

and then we sequence them, massively parallel.

然后进行大规模同时测序

Then we bring that into software and reassemble it,

然后用软件

重新合成并给你解读

and tell you what the story is.

为了让你更直观地了解

So to give you a picture of what this looks like,

the Human Genome Project: 3 gigabases, right?

人类基因组测序工程：3GB，

在这样的机器上测序：

One run on one of these modern machines: 200 gigabases in a week.

一周可完成200GB

And that 200 is going to change to 600 this summer,

这个夏天将有望提升至600

and there's no sign of this pace slowing.

并且这种增长没有放缓的趋势

The price of a base, to sequence a base,

所以每个碱基测序的价钱

has fallen 100 million times.

下降了一千万倍

That's the equivalent of you filling up your car with gas in 1998,

这就像你1998年给车加满油

等到2011年

waiting until 2011,

and now you can drive to Jupiter and back twice.

能到木星两个来回

(Laughter)

（笑声）

World population,

世界人口

PC配置

PC placements,

the archive of all of medical literature,

医学文献档案

Moore's law,

摩尔定律

the old way of sequencing,

旧的测序方式，然后是这些新玩意

and here's all the new stuff.

各位，这是个对数尺度

Guys, this is a long scale;

you don't typically see lines that go up like that.

你不会常看到趋势像那样上升

So the worldwide capacity to sequence human genomes

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

is something like 50,000 to 100,000 human genomes this year.

这是依据被配置的机器估算的

We know this based on the machines that are being placed.

而这在未来可能会

This is expected to double, triple or maybe quadruple

year over year for the foreseeable future.

每年翻两番，三番，甚至四番

In fact, there's one lab in particular

实际上，有一个实验室

that represents 20 percent of all that capacity:

具备所有测序能力中的百分之二十

It's called the Beijing Genomics Institute.

就是华大基因

The Chinese are absolutely winning this race to the new Moon, by the way.

中国人毫无疑问正在领跑这场新的登月竞赛

What does this mean for medicine?

这对药学来说什么意义呢？

So a woman, age 37,

如果一个37岁的女性

她患有II期ER阳性乳腺癌

presents with stage 2 estrogen receptor-positive breast cancer.

She is treated with surgery, chemotherapy and radiation.

她正在接受手术治疗，化疗和放射治疗

She goes home.

她回家了

Two years later,

2年后，她发现患上III期C卵巢癌

she comes back with stage 3C ovarian cancer, unfortunately;

不幸的是，再次接受手术和化疗

treated again with surgery and chemotherapy.

She comes back three years later at age 42

3年后她42岁

又患上卵巢癌，接受更多的化疗

with more ovarian cancer, more chemotherapy.

Six months later,

6个月后

she comes back with acute myeloid leukemia.

她患上急性髓性白血病

She goes into respiratory failure and dies eight days later.

最后呼吸衰竭八天后死亡

So first: the way in which this woman was treated,

首先她接受的10年治疗

in as little as 10 years, will look like bloodletting.

基本就是放血

And it's because of people like my colleague, Rick Wilson,

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

at the Genome Institute at Washington University,

who decided to take a look at this woman postmortem.

决定对她尸检

他进行测序，他取了皮肤细胞，健康的皮肤

And he took skin cells, healthy skin

and cancerous bone marrow,

和癌化的骨髓

and sequenced the whole genomes of both of them

他测定两者的所有基因组

区区几周后

in a couple of weeks, no big deal.

Then he compared those two genomes in software,

他用软件对比两组基因组

and what he found, among other things,

他发现了

was a deletion -- a 2,000-base deletion across three billion bases

30亿碱基里

有两千个碱基的丢失

in a particular gene called TP53.

这是在一个叫TP53的基因上

如果这个基因发生有害突变

If you have this deleterious mutation in this gene,

you're 90 percent likely to get cancer in your life.

就有百分之九十的可能患癌

So unfortunately, this doesn't help this woman,

很不幸这没能帮到这位女性

but it does have severe -- profound, if you will --

但这对她的家人来说

implications to her family.

是很重要深刻的启示

如果他们有同样的突变

I mean, if they have the same mutation,

and they get this genetic test and they understand it,

他们接受基因测试然后了解到该情况

then they can get regular screens and can catch cancer early,

他们就可以接受常规检查并早点发现病症

and potentially live a significantly longer life.

从而可以大大延长生命

Let me introduce you to the Beery twins,

让我来介绍毕瑞兄妹

diagnosed with cerebral palsy at the age of two.

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

Their mom is a very brave woman who didn't believe it;

她不相信诊断符合症状

the symptoms weren't matching up.

通过她不懈努力和网上搜索

And through some heroic efforts and a lot of Internet searching,

她说服了医疗人员

she was able to convince the medical community

他们患是另一种病

that, in fact, they had something else.

多巴反应性肌张力失常

They had dopa-responsive dystonia.

And so they were given L-Dopa,

所以采用L－多巴治疗

and their symptoms did improve,

他们的病情确实有所改善

but they weren't totally asymptomatic.

但是并没有完全消除

Significant problems remained.

仍然存在严重的问题

Turns out the gentleman in this picture is a guy named Joe Beery,

照片中的男士叫乔･毕瑞

很幸运地他是

who was lucky enough to be the CIO

一家叫做生命科技的公司的首席信息官

of a company called Life Technologies.

这家公司是

They're one of two companies

that makes these massive whole-genome sequencing tools.

提供基因组测序设备的两大供应商之一

And so he got his kids sequenced.

所以他测定他的孩子（的基因）

What they found was a series of mutations in a gene called SPR,

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

which is responsible for producing serotonin, among other things.

So on top of L-Dopa, they gave these kids a serotonin precursor drug,

所以除了L－多巴，他们也用血清素前体药物辅以治疗

and they're effectively normal now.

孩子们恢复正常了

Guys, this would never have happened without whole-genome sequencing.

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

At the time -- this was a few years ago -- it cost $100,000.

如今是一万美元，明年会是一千

Today it's $10,000, next year, $1,000,

后年是一百

the year after, $100, give or take a year.

就是这么快

That's how fast this is moving.

这是小尼克

So here's little Nick --

他喜欢蝙蝠侠和水枪

likes Batman and squirt guns.

And it turns out Nick shows up at the children's hospital

尼克去儿童医院接受治疗

with this distended belly, like a famine victim.

他的肚子涨得像饥荒儿童一样

And it's not that he's not eating; it's that when he eats,

这不是因为他不吃

而是他吃的时候，他的肠子就打开

his intestine basically opens up and feces spill out into his gut.

废物进入腹腔

在经历了无数手术后

So a hundred surgeries later,

he looks at his mom and says, "Mom, please pray for me.

他看着妈妈说“妈妈，

为我祈祷吧，我十分痛苦“

I'm in so much pain."

His pediatrician happens to have a background in clinical genetics

他的儿科医生恰好有临床遗传学方面的背景

and he has no idea what's going on,

他不知道问题出在哪儿

but he says, "Let's get this kid's genome sequenced."

他说”让我们给他做基因组测序吧“

And what they find is a single-point mutation

然后他们在控制程序性细胞死亡的基因上

in a gene responsible for controlling programmed cell death.

发现一个单点突变

So the theory is that he's having some immunological reaction

所以根源就是他对

to what's going on -- to the food, essentially.

食物有种免疫反应

And that's a natural reaction, which causes some programmed cell death,

这是种自然反应，它会导致程序性细胞死亡

but the gene that regulates that down is broken.

但这个基因的此种功能出现问题

所以对于这个问题

And so this informs, among other things, of course,

他接受了骨髓移植的治疗

a treatment for bone marrow transplant, which he undertakes.

9个月艰难的康复期后

And after nine months of grueling recovery,

他能吃A1沙司了

he's now eating steak with A1 sauce.

（笑声）

(Laughter)

The prospect of using the genome as a universal diagnostic

利用基因组

作为万能诊断方法的前景

is upon us today.

正在到来

就是今天，就在这里

Today. It's here.

这对这屋子里的每一个人来说

And what it means for all of us

is that everybody in this room could live an extra 5, 10, 20 years,

意味着我们可以多活十到二十年

just because of this one thing.

就是因为这项技术

Which is a fantastic story,

这是个神奇的故事

unless you think about humanity's footprint on the planet,

当然还有人类遍布全球的足迹

and our ability to keep up food production.

和我们追赶粮食产量的能力

不过

So it turns out

that the very same technology is also being used to grow new lines

这项技术

同样可以被利用于

of corn, wheat, soybean and other crops

种植新型玉米，麦子，大豆和其他粮食

that are highly tolerant of drought, of flood,

能够抵抗干旱和洪水

of pests and pesticides.

害虫和杀虫剂

Now, look --

随着人口不断增长

as long as we continue to increase the population,

我们会不得不使用转基因产品

we'll have to continue to grow and eat genetically modified foods.

这是我的唯一立场

And that's the only position I'll take today.

Unless there's anybody in the audience

除非观众中有人

who'd like to volunteer to stop eating?

决定绝食

不，没人会

None, not one.

This is a typewriter,

这是个打字机

a staple of every desktop for decades.

数十年前每个书桌上都有一个

And, in fact, the typewriter was essentially deleted by this thing.

实际上，打字机完全被这个取代了

And then more general versions of word processors came about.

然后是更多代文字处理器面世

But ultimately, it was a disruption on top of a disruption.

不过，最令人措手不及的

It was Bob Metcalfe inventing the Ethernet,

还是鲍勃･梅得卡夫发明了以太网

and the connection of all these computers

电脑的联网

that fundamentally changed everything.

革命性地改变了一切

Suddenly we had Netscape, we had Yahoo.

突然我们就有了Netscape，雅虎

And we had, indeed, the entire dot-com bubble.

然后是整个互联网的泡沫经济

(Laughter)

（笑声）

Not to worry though,

不过别担心

that was quickly rescued by the iPod, Facebook

iPod, Facebook又拯救了我们

and, indeed, Angry Birds.

当然还有愤怒地小鸟

(Laughter)

（笑声）

这就是我们今天所处（的环境）

Look, this is where we are today.

This is the genomic revolution today. This is where we are.

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：

What I'd like you to consider is:

如果这些点不是代表你的基因的碱基

What does it mean

when these dots don't represent the individual bases of your genome,

而是整个星球上基因相连

but they connect to genomes all across the planet?

这意味着什么？

I just recently had to buy life insurance, and I was required to answer:

我不久前才买了人身保险

我被这样问道：

A. I have never had a genetic test;

A.我从来没有进行过基因测试，B.我有过，没戏了

B. I've had one, here you go;

C.我有过但我不说出来

or C. I've had one and I'm not telling.

很幸运，我还能选A

Thankfully, I was able to answer A,

and I say that honestly, in case my life insurance agent is listening.

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？

But what would have happened if I had said C?

Consumer applications for genomics will flourish.

基因组学的消费需求将大大增加

你想不想知道

Do you want to see if you're genetically compatible

你跟女友的基因是否兼容？当然

with your girlfriend?

DNA sequencing on your iPhone? There's an app for that.

要不要在你的iPhone上基因测序？有这么一个应用

(Laughter)

（笑声）

Personalized genomic massage, anyone?

有人想要个人定制的基因学按摩吗？

如今已经有个实验室

There's already a lab today that tests for allele 334 of the AVPR1 gene,

为AVPR1基因上的等位基因334测序

所谓的欺骗基因

the so-called cheating gene.

谁今天是和你重要的另一半一起来的

(Laughter)

So anybody who's here today with your significant other,

只要转过去，刮下他／她的口腔

just turn over to them, swab their mouth, send it to the lab

寄到那个实验室你就知道了

and you'll know for sure.

（笑声）

(Laughter)

你想不想选一个

Do you really want to elect a president

可能患心肌病的总统？

whose genome suggests cardiomyopathy?

假设，现在是2016年

Think of it -- it's 2016,

竞选人不仅公开

and the leading candidate releases

她四年的税后申报

not only her four years of back-tax returns,

还有她的个人基因组

but also her personal genome.

看上去很不错

And it looks really good.

Then she challenges all her competitors to do the same.

然后她要求其他的竞争者也这么做

你觉得这不可能发生？

Do you think that's not going to happen?

你觉得这会帮到约翰･麦凯恩？

Do you think it would have helped John McCain?

（笑声）

(Laughter)

观众里有多少人

How many people in the audience have the last name Resnick, like me?

跟我同一个姓，雷斯尼克？请举手

Raise your hand.

有人是吗？ 没有

Anybody? Nobody.

明显，有一两个

Typically, there's one or two.

So my father's father was one of 10 Resnick brothers.

我父亲是雷斯尼克10兄弟种的一个

他们相互不喜欢

They all hated each other, and all moved to different parts of the planet.

他们移居到这世界上不同的角落

所以好比

So it's likely I'm related to every Resnick that I ever meet,

我与我遇到过的雷斯尼克都有关系，但我不确定

but I don't know.

So imagine if my genome were De-identified, sitting in software,

试想如果我的基因组被确定，保存在软件里

And a third cousin's genome was also sitting there,

一个三表兄弟的基因组也是

有软件可以对比两个（样本）

and there was software that could compare the two

并且联系上

and make these associations.

Not hard to imagine. My company has software that does this right now.

不难想像，我的公司就有这样的软件

那么再像一下

Imagine one more thing,

that that software is able to ask both parties for mutual consent:

如果软件可向双方征询同意书

"Would you be willing to meet your third cousin?"

“你想不想与你的三表兄见面？”

如果两人都说是

And if we both say yes -- voilà!

Welcome to Chromosomally LinkedIn.

耶！欢迎来到染色体LinkedIn网站

(Laughter)

（笑声）

Now this is probably a good thing, right?

这也许是个好事

Bigger clan gatherings and so on.

你可以有个大家族

But maybe it's a bad thing as well.

也可能是坏事

How many fathers in the room? Raise your hands.

这屋子里有多少父亲？请举手

OK, so experts think that one to three percent of you

好的，专家认为你们中间百分之一到三的人

are not actually the father of your child.

并不是你孩子的父亲

(Laughter)

（笑声）

Look --

这个－

(Laughter)

（笑声）

These genomes, these 23 chromosomes,

这些基因组，这23个染色体

they don't in any way represent the quality of our relationships

它们并不代表我们人际关系的质量

or the nature of our society -- at least not yet.

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

And like any new technology,

都取决与人类自己

it's really in humanity's hands

to wield it for the betterment of mankind

是否用于对人类有益的一面

or not.

所以我强烈期望你们所有人醒悟

And so I urge you all to wake up and to tune in

and to influence the genomic revolution that's happening all around you.

并参与到这场发生在你们周围的基因革命

谢谢

Thank you.

(Applause)

（鼓掌）