Richard Resnick: Welcome to the genomic revolution

譯者: Boyang Zhu 審譯者: Wang-Ju Tsai

女士們先生們，

Ladies and gentlemen,

I present to you the human genome.

我為大家展示一下人類基因組。

(Applause)

（掌聲）

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

染色體一，左上角

性染色體在右下角。

Women have two copies of that big X chromosome;

女生有兩份大的X染色體；

男生有一份X染色體

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

還有一份小的Y染色體。

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

很抱歉各位男士，讓你們有所不同的只是那一個小東西。

So if you zoom in on this genome,

如果我們放大這個基因組的圖片，

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

會看到雙螺旋結構

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

生命的編碼是由四個生化字符編寫出來，

我們稱之為基對：

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.

人類基因組有多少基對呢？ 30億。

Is that a big number?

這是一個很大的數字嗎？

Well, everybody can throw around big numbers.

每個人都可以隨便講一些很大的數字出來。

But in fact, if I were to place one base

如果我把這1280像素高800像素寬的螢幕上

on each pixel of this 1280x800-resolution screen,

每一個像素都用一個基對替換

我們需要3000塊這麼大的螢幕來觀察這基因組

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

所以這個數字真的是很大。

So it's really quite big.

And perhaps because of its size,

或許是因為這麼大

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

有一群人有Y染色體的人

decided they would want to sequence it.

決定想要把為它排序

(Laughter)

(笑聲)

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

15年前開始，花費了40億美金後

the genome was sequenced and published.

對基因組的排序終於完成並發表。

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

2003年，最終的版本發表，人們繼續對它的研究。

這一切都是在這樣的一台儀器上完成的。

That was all done on a machine like this.

每排序一個基對花費一美元左右

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

而且也是非常慢的一種做法。

Well, folks, I'm here to tell you

但是我要告訴大家

that the world has completely changed,

這世界已經發生了天翻地覆的變化

and none of you know about it.

然而你們卻都渾然不覺。

So now what we do is take a genome,

現在我們把一個基因組

we make maybe 50 copies of it,

複製50份

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

然後把他們切割為50基對

and then we sequence them, massively parallel.

接著我們就對他們進行大量並行地排序。

Then we bring that into software and reassemble it,

然後將結果輸入到軟體中

加以組合然後我們可以得出結論。

and tell you what the story is.

給大家看一張圖片來瞭解

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

the Human Genome Project: 3 gigabases, right?

人類基因組計畫：30億基對

在這些儀器上進行排序

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

每週可以完成2000億基對。

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

而且這個夏天它的速度會變成6000億基對

and there's no sign of this pace slowing.

這速度上的進展絲毫沒有減慢的跡象。

The price of a base, to sequence a base,

對一個基對排序的價格

has fallen 100 million times.

已經下跌了一億倍。

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

這就相當於你在1998年給汽車加滿一次油的錢

放到2011年

waiting until 2011,

and now you can drive to Jupiter and back twice.

可以讓你在地球和木星之間來回開2次。

(Laughter)

｛笑聲｝

World population,

世界人口，

電腦普及，

PC placements,

the archive of all of medical literature,

所以醫療文獻的存檔，

Moore's law,

摩爾定律，

the old way of sequencing,

早期的排序方法，這是新的技術。

and here's all the new stuff.

這是一個按指數擴大的情況；

Guys, this is a long scale;

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

你通常是不會看到這樣的走勢的。

So the worldwide capacity to sequence human genomes

全世界用於人類基因組測序的能力

可以在今年做到5萬到10萬個人類基因組。

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

我們是從已經投入應用的儀器來判斷這個數字。

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

在可預見的未來裏每年這個數字都會翻倍，

This is expected to double, triple or maybe quadruple

year over year for the foreseeable future.

或是以三倍甚至四倍的速度增長。

In fact, there's one lab in particular

有一個實驗室

that represents 20 percent of all that capacity:

佔據了全世界測序能力的20％。

It's called the Beijing Genomics Institute.

它叫做“華大基因”。

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

中國在這場新的“登月競賽”中處於領先。

What does this mean for medicine?

對於醫學這意味著甚麼呢？

So a woman, age 37,

有一個37歲的女性。

她出現了階段2的雌激素受阻體陽性乳腺癌。

presents with stage 2 estrogen receptor-positive breast cancer.

She is treated with surgery, chemotherapy and radiation.

經歷了手術，化療和放射性治療

She goes home.

回到了家裡。

Two years later,

兩年以後她又發現了三C期的卵巢癌。

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

她又接受了手術和化療，不幸的是

treated again with surgery and chemotherapy.

She comes back three years later at age 42

三年後她42歲，又發現了更多的卵巢癌

回到醫院，再接受更多的化療。

with more ovarian cancer, more chemotherapy.

Six months later,

6個月後，

she comes back with acute myeloid leukemia.

她又患上了急性骨髓性白血病

She goes into respiratory failure and dies eight days later.

最終因呼吸道衰竭在8天以後逝世。

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

在短短的10年中，這名婦女接受的治療

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

將會看起來如同放血一般。

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

因為我在華盛頓大學

基因研究院的同事Rick Wilson

at the Genome Institute at Washington University,

who decided to take a look at this woman postmortem.

決定要研究一下這名婦女的遺體進行檢驗

他提取了她正常皮膚細胞和發生癌變的

And he took skin cells, healthy skin

and cancerous bone marrow,

骨髓細胞並進行測序

and sequenced the whole genomes of both of them

在幾周的時間里，他對兩個基因組

進行了徹底的排序。

in a couple of weeks, no big deal.

Then he compared those two genomes in software,

然後在軟體中比對這兩組基因

and what he found, among other things,

他在30億基對中的

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

一個叫做TP53的基因上

發現了一段

in a particular gene called TP53.

2000基對的基因缺損。

如果你在這個基因上有此類缺損的異變，

If you have this deleterious mutation in this gene,

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

你一生中有90%的可能性會患上癌症。

So unfortunately, this doesn't help this woman,

不幸的是這個發現對這婦女沒有任何幫助，

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

但是這對她的家人，

implications to her family.

有非常重要的影響。

如果他們有相同的異變，

I mean, if they have the same mutation,

and they get this genetic test and they understand it,

接受這基因檢測，並對它有所瞭解，

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

他們可以定時地做篩檢，及早發現癌症

and potentially live a significantly longer life.

藉此可能大大延長壽命。

Let me introduce you to the Beery twins,

請讓我來向大家介紹Beery兄弟，

diagnosed with cerebral palsy at the age of two.

在2歲時候被診斷出大腦性癱瘓。

他們的母親是一位非常勇敢的女性

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

她不相信這是真正的病因。實際症狀與診斷並不相符，

the symptoms weren't matching up.

通過英勇的努力與大量的網上搜索，

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

她成功地說服醫療人員

she was able to convince the medical community

實際上孩子患上的是其他疾病。

that, in fact, they had something else.

他們所患的是多巴反應性肌張力障礙。

They had dopa-responsive dystonia.

And so they were given L-Dopa,

於是對他們使用了左旋多巴，

and their symptoms did improve,

症狀的確有所改善，

but they weren't totally asymptomatic.

但是沒有完全消除。

Significant problems remained.

嚴重的問題仍然存在。

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

幸運的是 照片裏有一位叫做Joe Beery男士,

他在一家叫做生命科技的公司

who was lucky enough to be the CIO

擔任首席資訊長的職務。

of a company called Life Technologies.

他們是現有的兩家

They're one of two companies

that makes these massive whole-genome sequencing tools.

開發大量全基因組測序工具的公司之一。

And so he got his kids sequenced.

他將自己孩子的基因進行測序。

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

結果在一個叫做SPR的基因里發現一系列異變

這個基因負責產生的物質裏包括血清素。

which is responsible for producing serotonin, among other things.

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

所以在左旋多巴的基礎上他們再給這些孩子使用血清素激發藥物。

and they're effectively normal now.

現在他們過上完全正常的生活。

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

沒有全基因組測序，這樣的事情永遠不可能實現。

在幾年前，全基因組測序要花費10萬美元。

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

今天的價格是一萬美元，明年就是一千美元。

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

到了後年或者大後年可能就是100美元。

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

價格移動的就是如此之快。

That's how fast this is moving.

這是小Nick.

So here's little Nick --

喜歡蝙蝠俠與水槍。

likes Batman and squirt guns.

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

Nick來到兒童醫院

with this distended belly, like a famine victim.

他的肚子腫脹地像營養不良的小孩

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

他並不是沒有吃東西

而是無論他吃甚麼，腸道都會自動打開

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

排泄物溢出到他的體內。

經歷了無數的手術後，

So a hundred surgeries later,

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

他看著他的媽媽說：媽媽，

請為我祈禱，真是太疼了。“

I'm in so much pain."

His pediatrician happens to have a background in clinical genetics

他的兒童科醫師恰巧有臨床遺傳學的背景

and he has no idea what's going on,

他不知道病因到底是甚麼

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

但是他決定為這個孩子做基因測序。

And what they find is a single-point mutation

他發現的是在一個控制細胞死亡

in a gene responsible for controlling programmed cell death.

的基因上有一處單點變異

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

原因就是他的身體對食物

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

產生了一種會導致程序性細胞死亡的

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

免疫性反應，這原本很正常一種的反應。

but the gene that regulates that down is broken.

但是管控這個機制的基因失效了。

這個結果使醫院在對他的

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

治療方案中加入了骨髓移植手術，

a treatment for bone marrow transplant, which he undertakes.

在經過9個月迅速地恢復後，

And after nine months of grueling recovery,

他現在在吃沾著A1醬汁的牛排了。

he's now eating steak with A1 sauce.

（笑聲）

(Laughter)

The prospect of using the genome as a universal diagnostic

今天使用基因組來

作為普遍診斷的前景

is upon us today.

已經來到我們身邊

今天，已經是可行的了

Today. It's here.

對我們所有人這意味著

And what it means for all of us

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

額外的5年，10年，20年的壽命

just because of this one thing.

就是這一項技術。

Which is a fantastic story,

真是一個美妙的故事，

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

你如果不去想到人類在地球上占有的空間

and our ability to keep up food production.

以及我們如何提高食物產能等等這些問題的話

結果就是

So it turns out

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

同樣的技術

也能用來製造新一代的

of corn, wheat, soybean and other crops

對乾旱，洪水，害蟲和殺蟲劑

that are highly tolerant of drought, of flood,

有超強抵抗力的玉米，小麥，

of pests and pesticides.

大豆和其他糧食。

Now, look --

只要我們的人口繼續在增長，

as long as we continue to increase the population,

我們就必須培養和食用更多的轉基因食物，

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

這是我今天唯一的立場。

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

Unless there's anybody in the audience

除非觀眾里有人

who'd like to volunteer to stop eating?

自願不再吃東西？

沒有，一個都沒有。

None, not one.

This is a typewriter,

這是一個打字機，

a staple of every desktop for decades.

數十年來，所有辦公桌上的主要用品之一。

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

實際上，打字機基本上被這台設備淘汰了。

And then more general versions of word processors came about.

然後更普遍的文字處理機出現了。

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

最終，在顛覆性的技術上出現了更顛覆性的技術。

It was Bob Metcalfe inventing the Ethernet,

Bob Metcalfe發明了以太網

and the connection of all these computers

連接起了所有電腦

that fundamentally changed everything.

徹底地改變了一切。

Suddenly we had Netscape, we had Yahoo.

突然間我們有了Netscape,然後有了Yahoo

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

再然後我們有了整個網路泡沫。

(Laughter)

（笑聲）

Not to worry though,

不過不用擔心，

that was quickly rescued by the iPod, Facebook

很快地就被Ipod，Facebook

and, indeed, Angry Birds.

和憤怒的小鳥（angry bird ）拯救了

(Laughter)

（笑聲）

這就是我們今天所處的位置。

Look, this is where we are today.

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

這就是今天的基因革命。

我希望你們思考的是：

What I'd like you to consider is:

當這些不僅僅代表

What does it mean

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

你個人基因組的基對，而是與全世界的

but they connect to genomes all across the planet?

基因組聯繫再一起意味著甚麼？

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

我最近剛買了人身保險。

我被要求回答：

A. I have never had a genetic test;

A 我從沒有過基因測試，B 我有過基因測試，

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

和C 我有過但是不告訴你。

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

還好我可以選A，

Thankfully, I was able to answer A,

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

我是非常誠實地在講，以防我的保險經紀人在聽這個演講。

但是如果我選了C會怎樣？

But what would have happened if I had said C?

Consumer applications for genomics will flourish.

與基因組相關的商業應用會遍地開花。

如果你想瞭解自己與女朋友基因上

Do you want to see if you're genetically compatible

是不是相適合？當然可以。

with your girlfriend?

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

DNA在你的Iphone上進行測序？也有一個app可以做到。

(Laughter)

（笑聲）

Personalized genomic massage, anyone?

有誰想做個個人基因按摩嗎？

今天已經有實驗室

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

在測試AVPR1基因上的allele 334，

就是所謂的欺騙基因。

the so-called cheating gene.

現場任何人帶了你的另一半來的話，

(Laughter)

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

轉向他們並在他們口中取些樣本，

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

送到實驗室你就會知道了。

and you'll know for sure.

（笑聲）

(Laughter)

你想選舉一位基因上表現出

Do you really want to elect a president

有心肌病隱患的總統嗎？

whose genome suggests cardiomyopathy?

想像一下現在是2016年

Think of it -- it's 2016,

優勢的總統競選人不僅

and the leading candidate releases

發佈了她過去四年中的退稅情況，

not only her four years of back-tax returns,

也公開她的個人基因組

but also her personal genome.

它看起來非常好。

And it looks really good.

Then she challenges all her competitors to do the same.

接著這位競選人也要求她的競爭對手做同樣的事情

你難道認為這一定不會發生？

Do you think that's not going to happen?

你覺得這會幫助麥凱恩嗎？

Do you think it would have helped John McCain?

（笑聲）

(Laughter)

在場觀眾中有多少人

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

有和我一樣的姓氏Resnick?請舉起手來。

Raise your hand.

有嗎？沒有。

Anybody? Nobody.

通常會有一兩個。

Typically, there's one or two.

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

我父親的父親是10個Resnick兄弟中的一名。

他們都互討厭，

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

分散到了全世界各地。

所以我可能和任何一個我遇到的

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

Resnick是遠親關係，只是我不知道而已。

but I don't know.

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

想像一下如果我的基因被辨識後紀錄在軟體中，

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

而我的一個表兄的基因也被紀錄下來

然後有軟體可以比較這兩組基因

and there was software that could compare the two

並做出關連。

and make these associations.

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

不難想像，我公司里現在就有這樣的軟體

再想像一下另一件事：

Imagine one more thing,

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

這個軟體可以徵求雙方的同意

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

你希望與你的三表兄相見嗎？

如果我們都同意，

And if we both say yes -- voilà!

Welcome to Chromosomally LinkedIn.

哇啦！歡迎來到染色體Linkedin.

(Laughter)

（笑聲）

Now this is probably a good thing, right?

這應該是一件好事，對嗎？

Bigger clan gatherings and so on.

集合更多的家族成員和其他可能性，

But maybe it's a bad thing as well.

但是這也可能是一件壞事。

How many fathers in the room? Raise your hands.

房間里有多少做父親的？舉起手來。

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

Okay,有專家認為你們中有1％到3％

are not actually the father of your child.

並不是自己孩子的親生父親。

(Laughter)

（笑聲）

Look --

這個－

(Laughter)

（笑聲）

These genomes, these 23 chromosomes,

這些基因組，這23對染色體，

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

他們並不能反應人與人之間的關係或者我們

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

社會的天性－至少現在還不能。

和任何新興的技術一樣，

And like any new technology,

它完全取決與人類是否

it's really in humanity's hands

to wield it for the betterment of mankind

將它使用在對人類的有益處的地方。

or not.

我希望你們全都覺醒並關注

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.

影響這時刻發生在大家身邊的遺傳學革命

謝謝

Thank you.

(Applause)

（掌聲）