about the human genome and what that might mean,

在這之前我已經討論過這些計畫中的一部分，

and discovering new sets of genes.

關於人類基因體和它們的意義，

We're actually starting at a new point:

以及發現新的基因。

we've been digitizing biology,

我們事實上是在開啟一個新的轉捩點：

and now we're trying to go from that digital code

我們在發展數位生物學。

into a new phase of biology

並且現在我們正嘗試從那些數位編碼走向

with designing and synthesizing life.

一個生物學的全新階段，

So, we've always been trying to ask big questions.

去設計與人工合成生命。

"What is life?" is something that I think many biologists

我們總是試著提出一些重要的基本問題。

have been trying to understand

例如“生命的本質是什麼?”我想是許多生物學家

at various levels.

不斷地嘗試在

We've tried various approaches,

在不同層面去理解的問題。

paring it down to minimal components.

我們嘗試了許多方法，

We've been digitizing it now for almost 20 years;

將生命解構成最小的組成單元。

when we sequenced the human genome,

到目前我們幾乎已經用了20年來將其數位化。

it was going from the analog world of biology

當我們在定序人類基因體時，

into the digital world of the computer.

我們從生物學的類比世界

Now we're trying to ask, "Can we regenerate life

走進了電腦的數位世界。

or can we create new life

現在我們試著去探討，我們是否能夠重新打造生命，

out of this digital universe?"

或者我們是否能從這個數位世界中，

This is the map of a small organism,

創造新的生命？

Mycoplasma genitalium,

這是一種微生物的基因序列圖，

that has the smallest genome for a species

名叫生殖道黴漿菌，

that can self-replicate in the laboratory,

它有著生物物種裡最小的基因體

and we've been trying to just see if

可以在實驗室中自我複製。

we can come up with an even smaller genome.

我們在試著看看是否

We're able to knock out on the order of 100 genes

我們能找到一種更小的基因體。

out of the 500 or so that are here.

我們能夠以數百基因的尺度去剔除

When we look at its metabolic map,

這500個基因，或者是你們現在所看到的。(生殖道黴漿菌只有521個基因)

it's relatively simple

但當我們來看它的新陳代謝的時候，

compared to ours --

這其實是相對簡單的

trust me, this is simple --

相對我們來說的話。

but when we look at all the genes

相信我，這算簡單的。

that we can knock out one at a time,

但當我們在看所有這些所有基因

it's very unlikely that this would yield

這些我們可以一次剔除一個的基因，

a living cell.

很難相信這種剔除基因的方法能產生出

So we decided the only way forward

一個活生生的細胞。

was to actually synthesize this chromosome

所以，我們認為唯一能繼續研究的方法

so we could vary the components

就是人工合成這些染色體

to ask some of these most fundamental questions.

以便我們能改變它的組成

And so we started down the road of:

來繼續問這些最基本的問題。

can we synthesize a chromosome?

於是我們開始沿著這條思路往下走

Can chemistry permit making

“我們能人工合成染色體嗎？”

these really large molecules

化學方法真的可以讓我們製造

where we've never been before?

這些我們從未合成過的

And if we do, can we boot up a chromosome?

超大分子嗎？

A chromosome, by the way, is just a piece of inert chemical material.

而且，就算我們可以，我們能啟動它嗎？

So, our pace of digitizing life has been increasing

染色體，順便說下，只是一些無活性的化學物質。

at an exponential pace.

我們來看，我們將生命數位化的的步調不斷地

Our ability to write the genetic code

以指數成長。

has been moving pretty slowly

我們編寫基因編碼的能力

but has been increasing,

進步得卻非常緩慢，

and our latest point would put it on, now, an exponential curve.

不過也還是在增加的。

We started this over 15 years ago.

我們最近的研究將會把編寫基因的速度提升至指數曲線的程度。

It took several stages, in fact,

我們於15年前開始這項工作。

starting with a bioethical review before we did the first experiments.

實際上它經過了好幾個階段。

But it turns out synthesizing DNA

在我們做最初的試驗前，先進行了一次生物倫理學的評估。

is very difficult.

但結果是人工合成DNA

There are tens of thousands of machines around the world

是非常困難的。

that make small pieces of DNA --

全世界有十幾萬台設備

30 to 50 letters in length --

在製造小片斷的DNA，

and it's a degenerate process, so the longer you make the piece,

長度在30到50個字元，

the more errors there are.

DNA 的合成是一個衰減的過程，製造的片斷越是長，

So we had to create a new method

所產生的錯誤就越多。

for putting these little pieces together and correct all the errors.

所以我們得發展一種新的方法

And this was our first attempt, starting with the digital information

把這些小片斷組合在起並修正所有產生的錯誤。

of the genome of phi X174.

我們的第一次嘗試，從Phi X 174基因體（噬菌體）

It's a small virus that kills bacteria.

的數位資訊開始。

We designed the pieces, went through our error correction

它是一種能殺死細菌的小型病毒。

and had a DNA molecule

我們設計了它的基因片斷，並經過了錯誤校正，

of about 5,000 letters.

於是就擁有了一條

The exciting phase came when we took this piece of inert chemical

長約5,000字元的DNA。

and put it in the bacteria,

最令人興奮的階段是當我們把這段沒有活性的化學物質

and the bacteria started to read this genetic code,

放入細菌體內，

made the viral particles.

細菌開始讀取基因編碼，

The viral particles then were released from the cells

並製造了病毒粒子。

and came back and killed the E. coli.

接著病毒粒子從細菌中被釋放出來，

I was talking to the oil industry recently

再返回來殺死了細菌 (E.coli，大腸桿菌，革蘭氏陰性菌)。

and I said they clearly understood that model.

我最近與石油行業有一些交流，

(Laughter)

我覺得他們對這個模式理解得非常透徹。

They laughed more than you guys are. (Laughter)

（笑聲）

And so, we think this is a situation

他們比你們笑得大聲多了。

where the software can actually build its own hardware

因此我們認為這種情況實際上

in a biological system.

是一種軟體能在一個生物系統內

But we wanted to go much larger:

打造自己的硬體。

we wanted to build the entire bacterial chromosome --

但我們還想再擴大規模。

it's over 580,000 letters of genetic code --

我們希望製造整條細菌染色體。

so we thought we'd build them in cassettes the size of the viruses

一條超過580,000字元長度的基因編碼。

so we could actually vary the cassettes

我們認為應該在以病毒大小的基因卡匣中建造它們

to understand

這樣我們可以改變這些基因卡匣

what the actual components of a living cell are.

來理解

Design is critical,

一個活細胞的實際組成是什麼？

and if you're starting with digital information in the computer,

設計 (準確的掌握正確的資訊) 是非常重要的，

that digital information has to be really accurate.

並且如果你在電腦上開始使用數位資訊，

When we first sequenced this genome in 1995,

那這些數位資訊必須十分準確。

the standard of accuracy was one error per 10,000 base pairs.

當我們在1995年第一次定序這基因體時，

We actually found, on resequencing it,

準確率的標準是每10,000個鹽基對一個錯誤。

30 errors; had we used that original sequence,

實際上我們發現，在重新定序時，

it never would have been able to be booted up.

平均是30個錯誤。如果我們使用原先的序列，

Part of the design is designing pieces

這組基因永遠不可能被啟動。

that are 50 letters long

設計工作的一部分是

that have to overlap with all the other 50-letter pieces

設計50個字元長度的片斷

to build smaller subunits

並和其他的50字元長的片段相互重疊

we have to design so they can go together.

以構建較小的次單元。

We design unique elements into this.

我們要設計使他們能組合在一起。

You may have read that we put watermarks in.

因此我們在裡面設計了一個特別的元素。

Think of this:

你們可能聽說過我們在其中加入了浮水印。

we have a four-letter genetic code -- A, C, G and T.

想想看

Triplets of those letters

基因編碼有四個字元：A、C、G和T。

code for roughly 20 amino acids,

三個字元的不同組合

such that there's a single letter designation

編碼了大約20種氨基酸

for each of the amino acids.

而每種氨基酸有其相對應的

So we can use the genetic code to write out words,

基因編碼字元組合。

sentences, thoughts.

所以我們能使用基因編碼來撰寫詞彙

Initially, all we did was autograph it.

句子，想法。

Some people were disappointed there was not poetry.

最初，我們所做的就是用它來簽名。

We designed these pieces so

有些人有點失望我們沒用它來做首詩。

we can just chew back with enzymes;

我們設計了這些片斷

there are enzymes that repair them and put them together.

讓它能被酵素來裁切。

And we started making pieces,

這些酵素是用來修復他們並把他們組合在一起的。

starting with pieces that were 5,000 to 7,000 letters,

接著我們開始製造片斷，

put those together to make 24,000-letter pieces,

從7,000字元長度的片斷開始，

then put sets of those going up to 72,000.

把他們組合在一起製造出24,000字元長度的片斷，

At each stage, we grew up these pieces in abundance

再把幾組片斷合併，變成了長72,000字元的片斷。

so we could sequence them

在每個階段，我們大量產生了這些片斷

because we're trying to create a process that's extremely robust

因此我們可以給他們定序

that you can see in a minute.

因為我們希望發展出一個十分可靠的生產過程

We're trying to get to the point of automation.

等會兒你就將看見。

So, this looks like a basketball playoff.

我們試著將這些過程自動化

When we get into these really large pieces

這看起來就像是一場籃球賽的對戰圖

over 100,000 base pairs,

當這些非常大的片斷

they won't any longer grow readily in E. coli --

超過100,000鹽基對時

it exhausts all the modern tools of molecular biology --

他們就很難繼續在大腸桿菌裡長得更長了。

and so we turned to other mechanisms.

在試盡了各種現代分子生物學的工具後。

We knew there's a mechanism called homologous recombination

我們嘗試其他的方法。

that biology uses to repair DNA

我們知道有個機制叫同源重組，

that can put pieces together.

在生物學上用來修復DNA，

Here's an example of it:

它能把片斷組合在一起，

there's an organism called

這裡有一個例子。

Deinococcus radiodurans

有一種微生物名為

that can take three millions rads of radiation.

耐輻射奇異球菌

You can see in the top panel, its chromosome just gets blown apart.

能夠承受三百萬雷得 (rads, 輻射單位) 的輻射量。

Twelve to 24 hours later, it put it

你能看到在上圖中，它的染色體散佈在各個地方。

back together exactly as it was before.

暴露在輻射之後經過12到24小時，

We have thousands of organisms that can do this.

它將自己又組合回之前的原狀。

These organisms can be totally desiccated;

我們有數千種生物有這種能耐。

they can live in a vacuum.

這些生物能夠完全脫離水。

I am absolutely certain that life can exist in outer space,

他們能存活在真空中。

move around, find a new aqueous environment.

我完全確信外太空存在著生命，

In fact, NASA has shown a lot of this is out there.

他們四處游走，並找到一個新的有水的環境。

Here's an actual micrograph of the molecule we built

實際上，NASA已經展示過很多這樣的例子。

using these processes, actually just using yeast mechanisms

這是我們藉由上述程序所製造出來的染色體分子的真實顯微照片

with the right design of the pieces we put them in;

這些程序，事實上就是在酵母菌中放入我們正確設計的片斷

yeast puts them together automatically.

再利用酵母菌遺傳工程的方法

This is not an electron micrograph;

最後酵母菌會自動地將他們組合起來。

this is just a regular photomicrograph.

這並不是電子顯微照片；

It's such a large molecule

它僅僅是普通的光學顯微鏡。

we can see it with a light microscope.

這是如此之大的一個分子

These are pictures over about a six-second period.

我們可以直接用光學顯微鏡觀察它。

So, this is the publication we had just a short while ago.

這些是間隔約為六秒的照片。

This is over 580,000 letters of genetic code;

這是我們所發表的最新的研究成果。

it's the largest molecule ever made by humans of a defined structure.

這是超過580,000字元長的基因編碼。

It's over 300 million molecular weight.

這也是由人類設定結構並製造的最大的分子。

If we printed it out at a 10 font with no spacing,

它的分子量超過3億。

it takes 142 pages

如果我們以10號字體不間斷地將其列印出來。

just to print this genetic code.

總共需要142頁

Well, how do we boot up a chromosome? How do we activate this?

來列印這些基因編碼

Obviously, with a virus it's pretty simple;

好了，那我們該如何來啟動一段染色體，我們該如何活化它?

it's much more complicated dealing with bacteria.

顯然處理一個病毒非常簡單

It's also simpler when you go

處理一個細菌就複雜多了

into eukaryotes like ourselves:

以真核生物如我們人類來說，

you can just pop out the nucleus

啟動染色體也還算簡單。

and pop in another one,

你只需取出一個細胞核

and that's what you've all heard about with cloning.

然後放入另一個細胞中，

With bacteria and Archaea, the chromosome is integrated into the cell,

這就是大家所聽到的「複製」的方法。

but we recently showed that we can do a complete transplant

而在古細菌中，它們的染色體與整個細胞是一體的，

of a chromosome from one cell to another

但最近我們也顯示了我們可以做一個完整的移植

and activate it.

將染色體從一個細胞轉移到另一個細胞中

We purified a chromosome from one microbial species --

並活化它。

roughly, these two are as distant as human and mice --

我們從一種微生物中純化出染色體。

we added a few extra genes

大致上，這兩種之間的差別就如同人類和老鼠般。

so we could select for this chromosome,

我們加上了一些新的基因

we digested it with enzymes

這樣我們就能篩選這些染色體。

to kill all the proteins,

我們用酵素來分解掉

and it was pretty stunning when we put this in the cell --

染色體上所有的蛋白質。

and you'll appreciate

當我們將它放入細胞時發生的情況非常驚人

our very sophisticated graphics here.

你們應該會喜歡

The new chromosome went into the cell.

我們製作得非常精緻的示意圖:

In fact, we thought this might be as far as it went,

新的染色體進入細胞。

but we tried to design the process a little bit further.

實際上我們原以為這個過程就到此為止了。

This is a major mechanism of evolution right here.

但是我們試圖將這個過程設計得更深入一些。

We find all kinds of species

這是一個重要的演化機制。

that have taken up a second chromosome

我們發現所有接受了

or a third one from somewhere,

第二段染色體的物種

adding thousands of new traits

或來自其他地方的第三方染色體，

in a second to that species.

其自身增加了數千種新特徵

So, people who think of evolution

在一秒鐘內。

as just one gene changing at a time

原本人們以為在演化的過程中

have missed much of biology.

每次只會有一個基因發生變化

There are enzymes called restriction enzymes

的觀念忽略了生物的許多實際情況。

that actually digest DNA.

有一種酵素叫做限制酶

The chromosome that was in the cell

能夠分解DNA

doesn't have one;

原先細胞中的染色體中

the chromosome we put in does.

沒有這種酶

It got expressed and it recognized

而當我們置入一段擁有這種酶的染色體

the other chromosome as foreign material,

它表現了出來，並且辨認出

chewed it up, and so we ended up

另一段染色體是外來物質，

just with a cell with the new chromosome.

它就將其消化，最後我們就有了

It turned blue because of the genes we put in it.

一個包含有新的DNA的細胞

And with a very short period of time,

我們放入的基因導致它變成了藍色。

all the characteristics of one species were lost

在非常短的一段時間裡，

and it converted totally into the new species

所有的原先物種的特徵全部消失了，

based on the new software that we put in the cell.

並完全轉化成另一新物種

All the proteins changed,

基於我們放入細胞的新軟體。

the membranes changed;

所有的蛋白質都不一樣了，

when we read the genetic code, it's exactly what we had transferred in.

細胞膜也改變了 --

So, this may sound like genomic alchemy,

當我們讀取它的基因編碼，它正是我們轉入的那種。

but we can, by moving the software of DNA around,

這可能聽起來像基因體煉金術，

change things quite dramatically.

但我們的確能通過轉移DNA軟體，

Now I've argued, this is not genesis;

來劇烈地改變事物。

this is building on three and a half billion years of evolution.

現在，我要聲明這不是創世紀 --

And I've argued that we're about to perhaps

這是建立在35億年的演化上的

create a new version of the Cambrian explosion,

並且我認為我們可能

where there's massive new speciation

會創造新一版的寒武紀大爆發

based on this digital design.

出現大量的新物種

Why do this?

基於這種數位設計

I think this is pretty obvious in terms of some of the needs.

為什麼要這樣做？

We're about to go from six and a half

我認為出於一些需求我們這樣做的原因是非常明顯的。

to nine billion people over the next 40 years.

我們的人口將在接下來的40年中

To put it in context for myself:

從65億變成90億

I was born in 1946.

以我自己來舉例

There are now three people on the planet

我出生於1946年

for every one of us that existed in 1946;

現在世界上就變成了三個人

within 40 years, there'll be four.

對於我們中每一個從1946年就存在的人；

We have trouble feeding, providing fresh, clean water,

在接下來的四十年內，就變成了四個。

medicines, fuel

我們在為65億人提供食物，潔淨的淡水，

for the six and a half billion.

醫藥，燃料上

It's going to be a stretch to do it for nine.

都十分困難。

We use over five billion tons of coal,

換作90億人那更是難上加難了。

30 billion-plus barrels of oil --

我們使用超過50億頓的煤，

that's a hundred million barrels a day.

300多億桶的石油。

When we try to think of biological processes

也就是每天一億桶。

or any process to replace that,

當我們嘗試思考生物方法