Craig Venter: On the verge of creating synthetic life

譯者: Tom Lin 審譯者: Yi-Jyun Luo

You know, I've talked about some of these projects before --

在這之前我已經討論過這些計畫中的一部分，

about the human genome and what that might mean,

關於人類基因體和它們的意義，

and discovering new sets of genes.

以及發現新的基因。

We're actually starting at a new point:

我們事實上是在開啟一個新的轉捩點：

we've been digitizing biology,

我們在發展數位生物學。

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

並且現在我們正嘗試從那些數位編碼走向

into a new phase of biology

一個生物學的全新階段，

with designing and synthesizing life.

去設計與人工合成生命。

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

我們總是試著提出一些重要的基本問題。

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

例如“生命的本質是什麼?”我想是許多生物學家

have been trying to understand

不斷地嘗試在

at various levels.

在不同層面去理解的問題。

We've tried various approaches,

我們嘗試了許多方法，

paring it down to minimal components.

將生命解構成最小的組成單元。

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

到目前我們幾乎已經用了20年來將其數位化。

when we sequenced the human genome,

當我們在定序人類基因體時，

it was going from the analog world of biology

我們從生物學的類比世界

into the digital world of the computer.

走進了電腦的數位世界。

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

現在我們試著去探討，我們是否能夠重新打造生命，

or can we create new life

或者我們是否能從這個數位世界中，

out of this digital universe?"

創造新的生命？

This is the map of a small organism,

這是一種微生物的基因序列圖，

Mycoplasma genitalium,

名叫生殖道黴漿菌，

that has the smallest genome for a species

它有著生物物種裡最小的基因體

that can self-replicate in the laboratory,

可以在實驗室中自我複製。

and we've been trying to just see if

我們在試著看看是否

we can come up with an even smaller genome.

我們能找到一種更小的基因體。

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

我們能夠以數百基因的尺度去剔除

out of the 500 or so that are here.

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)

When we look at its metabolic map,

但當我們來看它的新陳代謝的時候，

it's relatively simple

這其實是相對簡單的

compared to ours --

相對我們來說的話。

trust me, this is simple --

相信我，這算簡單的。

but when we look at all the genes

但當我們在看所有這些所有基因

that we can knock out one at a time,

這些我們可以一次剔除一個的基因，

it's very unlikely that this would yield

很難相信這種剔除基因的方法能產生出

a living cell.

一個活生生的細胞。

So we decided the only way forward

所以，我們認為唯一能繼續研究的方法

was to actually synthesize this chromosome

就是人工合成這些染色體

so we could vary the components

以便我們能改變它的組成

to ask some of these most fundamental questions.

來繼續問這些最基本的問題。

And so we started down the road of:

於是我們開始沿著這條思路往下走

can we synthesize a chromosome?

“我們能人工合成染色體嗎？”

Can chemistry permit making

化學方法真的可以讓我們製造

these really large molecules

這些我們從未合成過的

where we've never been before?

超大分子嗎？

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

而且，就算我們可以，我們能啟動它嗎？

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

染色體，順便說下，只是一些無活性的化學物質。

So, our pace of digitizing life has been increasing

我們來看，我們將生命數位化的的步調不斷地

at an exponential pace.

以指數成長。

Our ability to write the genetic code

我們編寫基因編碼的能力

has been moving pretty slowly

進步得卻非常緩慢，

but has been increasing,

不過也還是在增加的。

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

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。

We started this over 15 years ago.

我們於15年前開始這項工作。

It took several stages, in fact,

實際上它經過了好幾個階段。

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

在我們做最初的試驗前，先進行了一次生物倫理學的評估。

But it turns out synthesizing DNA

但結果是人工合成DNA

is very difficult.

是非常困難的。

There are tens of thousands of machines around the world

全世界有十幾萬台設備

that make small pieces of DNA --

在製造小片斷的DNA，

30 to 50 letters in length --

長度在30到50個字元，

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

DNA 的合成是一個衰減的過程，製造的片斷越是長，

the more errors there are.

所產生的錯誤就越多。

So we had to create a new method

所以我們得發展一種新的方法

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

把這些小片斷組合在起並修正所有產生的錯誤。

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

我們的第一次嘗試，從Phi X 174基因體（噬菌體）

of the genome of phi X174.

的數位資訊開始。

It's a small virus that kills bacteria.

它是一種能殺死細菌的小型病毒。

We designed the pieces, went through our error correction

我們設計了它的基因片斷，並經過了錯誤校正，

and had a DNA molecule

於是就擁有了一條

of about 5,000 letters.

長約5,000字元的DNA。

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

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 put it in the bacteria,

放入細菌體內，

and the bacteria started to read this genetic code,

細菌開始讀取基因編碼，

made the viral particles.

並製造了病毒粒子。

The viral particles then were released from the cells

接著病毒粒子從細菌中被釋放出來，

and came back and killed the E. coli.

再返回來殺死了細菌 (E.coli，大腸桿菌，革蘭氏陰性菌)。

I was talking to the oil industry recently

我最近與石油行業有一些交流，

and I said they clearly understood that model.

我覺得他們對這個模式理解得非常透徹。

(Laughter)

（笑聲）

They laughed more than you guys are. (Laughter)

他們比你們笑得大聲多了。

And so, we think this is a situation

因此我們認為這種情況實際上

where the software can actually build its own hardware

是一種軟體能在一個生物系統內

in a biological system.

打造自己的硬體。

But we wanted to go much larger:

但我們還想再擴大規模。

we wanted to build the entire bacterial chromosome --

我們希望製造整條細菌染色體。

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

一條超過580,000字元長度的基因編碼。

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

我們認為應該在以病毒大小的基因卡匣中建造它們

so we could actually vary the cassettes

這樣我們可以改變這些基因卡匣

to understand

來理解

what the actual components of a living cell are.

一個活細胞的實際組成是什麼？

Design is critical,

設計 (準確的掌握正確的資訊) 是非常重要的，

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

並且如果你在電腦上開始使用數位資訊，

that digital information has to be really accurate.

那這些數位資訊必須十分準確。

When we first sequenced this genome in 1995,

當我們在1995年第一次定序這基因體時，

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

準確率的標準是每10,000個鹽基對一個錯誤。

We actually found, on resequencing it,

實際上我們發現，在重新定序時，

30 errors; had we used that original sequence,

平均是30個錯誤。如果我們使用原先的序列，

it never would have been able to be booted up.

這組基因永遠不可能被啟動。

Part of the design is designing pieces

設計工作的一部分是

that are 50 letters long

設計50個字元長度的片斷

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

並和其他的50字元長的片段相互重疊

to build smaller subunits

以構建較小的次單元。

we have to design so they can go together.

我們要設計使他們能組合在一起。

We design unique elements into this.

因此我們在裡面設計了一個特別的元素。

You may have read that we put watermarks in.

你們可能聽說過我們在其中加入了浮水印。

Think of this:

想想看

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

基因編碼有四個字元：A、C、G和T。

Triplets of those letters

三個字元的不同組合

code for roughly 20 amino acids,

編碼了大約20種氨基酸

such that there's a single letter designation

而每種氨基酸有其相對應的

for each of the amino acids.

基因編碼字元組合。

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

所以我們能使用基因編碼來撰寫詞彙

sentences, thoughts.

句子，想法。

Initially, all we did was autograph it.

最初，我們所做的就是用它來簽名。

Some people were disappointed there was not poetry.

有些人有點失望我們沒用它來做首詩。

We designed these pieces so

我們設計了這些片斷

we can just chew back with enzymes;

讓它能被酵素來裁切。

there are enzymes that repair them and put them together.

這些酵素是用來修復他們並把他們組合在一起的。

And we started making pieces,

接著我們開始製造片斷，

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

從7,000字元長度的片斷開始，

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

把他們組合在一起製造出24,000字元長度的片斷，

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

再把幾組片斷合併，變成了長72,000字元的片斷。

At each stage, we grew up these pieces in abundance

在每個階段，我們大量產生了這些片斷

so we could sequence them

因此我們可以給他們定序

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

因為我們希望發展出一個十分可靠的生產過程

that you can see in a minute.

等會兒你就將看見。

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

我們試著將這些過程自動化

So, this looks like a basketball playoff.

這看起來就像是一場籃球賽的對戰圖

When we get into these really large pieces

當這些非常大的片斷

over 100,000 base pairs,

超過100,000鹽基對時

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

他們就很難繼續在大腸桿菌裡長得更長了。

it exhausts all the modern tools of molecular biology --

在試盡了各種現代分子生物學的工具後。

and so we turned to other mechanisms.

我們嘗試其他的方法。

We knew there's a mechanism called homologous recombination

我們知道有個機制叫同源重組，

that biology uses to repair DNA

在生物學上用來修復DNA，

that can put pieces together.

它能把片斷組合在一起，

Here's an example of it:

這裡有一個例子。

there's an organism called

有一種微生物名為

Deinococcus radiodurans

耐輻射奇異球菌

that can take three millions rads of radiation.

能夠承受三百萬雷得 (rads, 輻射單位) 的輻射量。

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

你能看到在上圖中，它的染色體散佈在各個地方。

Twelve to 24 hours later, it put it

暴露在輻射之後經過12到24小時，

back together exactly as it was before.

它將自己又組合回之前的原狀。

We have thousands of organisms that can do this.

我們有數千種生物有這種能耐。

These organisms can be totally desiccated;

這些生物能夠完全脫離水。

they can live in a vacuum.

他們能存活在真空中。

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

我完全確信外太空存在著生命，

move around, find a new aqueous environment.

他們四處游走，並找到一個新的有水的環境。

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

實際上，NASA已經展示過很多這樣的例子。

Here's an actual micrograph of the molecule we built

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

using these processes, actually just using yeast mechanisms

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

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

再利用酵母菌遺傳工程的方法

yeast puts them together automatically.

最後酵母菌會自動地將他們組合起來。

This is not an electron micrograph;

這並不是電子顯微照片；

this is just a regular photomicrograph.

它僅僅是普通的光學顯微鏡。

It's such a large molecule

這是如此之大的一個分子

we can see it with a light microscope.

我們可以直接用光學顯微鏡觀察它。

These are pictures over about a six-second period.

這些是間隔約為六秒的照片。

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

這是我們所發表的最新的研究成果。

This is over 580,000 letters of genetic code;

這是超過580,000字元長的基因編碼。

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

這也是由人類設定結構並製造的最大的分子。

It's over 300 million molecular weight.

它的分子量超過3億。

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

如果我們以10號字體不間斷地將其列印出來。

it takes 142 pages

總共需要142頁

just to print this genetic code.

來列印這些基因編碼

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

好了，那我們該如何來啟動一段染色體，我們該如何活化它?

Obviously, with a virus it's pretty simple;

顯然處理一個病毒非常簡單

it's much more complicated dealing with bacteria.

處理一個細菌就複雜多了

It's also simpler when you go

以真核生物如我們人類來說，

into eukaryotes like ourselves:

啟動染色體也還算簡單。

you can just pop out the nucleus

你只需取出一個細胞核

and pop in another one,

然後放入另一個細胞中，

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

這就是大家所聽到的「複製」的方法。

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

而在古細菌中，它們的染色體與整個細胞是一體的，

but we recently showed that we can do a complete transplant

但最近我們也顯示了我們可以做一個完整的移植

of a chromosome from one cell to another

將染色體從一個細胞轉移到另一個細胞中

and activate it.

並活化它。

We purified a chromosome from one microbial species --

我們從一種微生物中純化出染色體。

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

大致上，這兩種之間的差別就如同人類和老鼠般。

we added a few extra genes

我們加上了一些新的基因

so we could select for this chromosome,

這樣我們就能篩選這些染色體。

we digested it with enzymes

我們用酵素來分解掉

to kill all the proteins,

染色體上所有的蛋白質。

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

當我們將它放入細胞時發生的情況非常驚人

and you'll appreciate

你們應該會喜歡

our very sophisticated graphics here.

我們製作得非常精緻的示意圖:

The new chromosome went into the cell.

新的染色體進入細胞。

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

實際上我們原以為這個過程就到此為止了。

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

但是我們試圖將這個過程設計得更深入一些。

This is a major mechanism of evolution right here.

這是一個重要的演化機制。

We find all kinds of species

我們發現所有接受了

that have taken up a second chromosome

第二段染色體的物種

or a third one from somewhere,

或來自其他地方的第三方染色體，

adding thousands of new traits

其自身增加了數千種新特徵

in a second to that species.

在一秒鐘內。

So, people who think of evolution

原本人們以為在演化的過程中

as just one gene changing at a time

每次只會有一個基因發生變化

have missed much of biology.

的觀念忽略了生物的許多實際情況。

There are enzymes called restriction enzymes

有一種酵素叫做限制酶

that actually digest DNA.

能夠分解DNA

The chromosome that was in the cell

原先細胞中的染色體中

doesn't have one;

沒有這種酶

the chromosome we put in does.

而當我們置入一段擁有這種酶的染色體

It got expressed and it recognized

它表現了出來，並且辨認出

the other chromosome as foreign material,

另一段染色體是外來物質，

chewed it up, and so we ended up

它就將其消化，最後我們就有了

just with a cell with the new chromosome.

一個包含有新的DNA的細胞

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

我們放入的基因導致它變成了藍色。

And with a very short period of time,

在非常短的一段時間裡，

all the characteristics of one species were lost

所有的原先物種的特徵全部消失了，

and it converted totally into the new species

並完全轉化成另一新物種

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

基於我們放入細胞的新軟體。

All the proteins changed,

所有的蛋白質都不一樣了，

the membranes changed;

細胞膜也改變了 --

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

當我們讀取它的基因編碼，它正是我們轉入的那種。

So, this may sound like genomic alchemy,

這可能聽起來像基因體煉金術，

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

但我們的確能通過轉移DNA軟體，

change things quite dramatically.

來劇烈地改變事物。

Now I've argued, this is not genesis;

現在，我要聲明這不是創世紀 --

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

這是建立在35億年的演化上的

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

並且我認為我們可能

create a new version of the Cambrian explosion,

會創造新一版的寒武紀大爆發

where there's massive new speciation

出現大量的新物種

based on this digital design.

基於這種數位設計

Why do this?

為什麼要這樣做？

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

我認為出於一些需求我們這樣做的原因是非常明顯的。

We're about to go from six and a half

我們的人口將在接下來的40年中

to nine billion people over the next 40 years.

從65億變成90億

To put it in context for myself:

以我自己來舉例

I was born in 1946.

我出生於1946年

There are now three people on the planet

現在世界上就變成了三個人

for every one of us that existed in 1946;

對於我們中每一個從1946年就存在的人；

within 40 years, there'll be four.

在接下來的四十年內，就變成了四個。

We have trouble feeding, providing fresh, clean water,

我們在為65億人提供食物，潔淨的淡水，

medicines, fuel

醫藥，燃料上

for the six and a half billion.

都十分困難。

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

換作90億人那更是難上加難了。

We use over five billion tons of coal,

我們使用超過50億頓的煤，

30 billion-plus barrels of oil --

300多億桶的石油。

that's a hundred million barrels a day.

也就是每天一億桶。

When we try to think of biological processes

當我們嘗試思考生物方法

or any process to replace that,

或者任何能替代它的方法，

it's going to be a huge challenge.

這會是一個巨大的挑戰。

Then of course, there's all that

接下來，當然，

CO2 from this material

這份資料是關於CO2

that ends up in the atmosphere.

被排放在大氣層中的二氧化碳。

We now, from our discovery around the world,

我們現在從全球各地的發現

have a database with about 20 million genes,

有了一個包含約兩千萬組基因的資料庫，

and I like to think of these as the design components of the future.

並且我樂於把它們看作是未來的設計元件。

The electronics industry only had a dozen or so components,

電機業只有十來種元件，

and look at the diversity that came out of that.

再看看從中能得到的多樣性。

We're limited here primarily

目前我們主要的限制來自於

by a biological reality

生物學的現實

and our imagination.

以及我們的想像力。

We now have techniques,

我們現在擁有這樣的技術，

because of these rapid methods of synthesis,

是因為有快速的人工合成方法

to do what we're calling combinatorial genomics.

能做出我們所謂的「組合基因體」。

We have the ability now to build a large robot

我們現在所擁有的製造一個大型機器人的能力

that can make a million chromosomes a day.

能讓我們每天製造一百萬個染色體。

When you think of processing these 20 million different genes

當你想著加工這兩千萬組不同的基因，

or trying to optimize processes

並嘗試去優化這些步驟

to produce octane or to produce pharmaceuticals,

以產生辛烷或者製造藥物，

new vaccines,

新的疫苗，

we can just with a small team,

我們就能改變，即使是一個小團隊，

do more molecular biology

完成更多的分子生物學工作

than the last 20 years of all science.

比過去20年科學史所做過的還多。

And it's just standard selection:

並且這只是標準選擇。

we can select for viability,

我們可以以生存能力來選擇，

chemical or fuel production,

化學或燃料生產，

vaccine production, etc.

疫苗生產等等。

This is a screen snapshot

這是一張螢幕截圖

of some true design software

截取的是一些我們

that we're working on to actually be able to sit down

實際坐下來工作時在電腦中

and design species in the computer.

真正用來設計物種的設計軟體。

You know, we don't know necessarily what it'll look like:

我們並不一定要知道它(設計的物種)看起來是怎樣。

we know exactly what their genetic code looks like.

我們確切地知道它們的基因編碼究竟是什麼樣的。

We're focusing on now fourth-generation fuels.

我們目前把焦點放在“第四代燃料”上。

You've seen recently, corn to ethanol

你們最近看到了將穀物轉化成乙醇

is just a bad experiment.

只是一個糟糕的試驗。

We have second- and third-generation fuels

很快我們將會擁有

that will be coming out relatively soon

第二及第三代燃料。

that are sugar, to much higher-value fuels

就是糖轉化成更高價值的燃料

like octane or different types of butanol.

例如辛烷或不同種類的丁醇。

But the only way we think that biology

但我們認為生物學唯一能

can have a major impact without

產生一個巨大影響的同時又不

further increasing the cost of food and limiting its availability

增加食物的支出與限制其可利用性的方法

is if we start with CO2 as its feedstock,

是在於我們是否能開始用二氧化碳作為它的原料。

and so we're working with designing cells to go down this road.

所以我們正在進行設計新的細胞能朝這條路發展下去。

And we think we'll have the first fourth-generation fuels

並且我們認為將會取得第一份第四代燃料

in about 18 months.

在18個月內。

Sunlight and CO2 is one method ...

陽光和二氧化碳是其中一個方法 --

(Applause)

（掌聲）

but in our discovery around the world,

-- 但我們從全世界各地的發現中，

we have all kinds of other methods.

我們還有許多種其他方法。

This is an organism we described in 1996.

這是一種微生物,1996年被記載

It lives in the deep ocean,

它生活在深海。

about a mile and a half deep,

大約1.5英里深，

almost at boiling-water temperatures.

幾乎是在沸騰的水溫中。

It takes CO2 to methane

它將二氧化碳轉化成甲烷

using molecular hydrogen as its energy source.

使用氫分子最為它的能量來源。

We're looking to see if we can take

我們在看是否能把

captured CO2,

收集到的二氧化染

which can easily be piped to sites,

它們非常方便就能被引進處理站，

convert that CO2 back into fuel

轉化成燃料，

to drive this process.

來驅動這個過程。

So, in a short period of time,

因此在很短的時間內，

we think that we might be able to increase

我們覺得我們或許可以增加對於"生命是什麼?"

what the basic question is of "What is life?"

的基本問題的理解。

We truly, you know,

我們的確

have modest goals

有著替換整個

of replacing the whole petrol-chemical industry --

石油化工行業的小小目標。

(Laughter) (Applause)

（笑聲）（掌聲）

Yeah. If you can't do that at TED, where can you? --

如果你不能在TED做到這些,哪里還有可能呢?

(Laughter)

（笑聲）

become a major source of energy ...

成為一項主要的能源。

But also, we're now working on using these same tools

並且我們也在使用同樣的工具

to come up with instant sets of vaccines.

製造了幾組即時疫苗。

You've seen this year with flu;

你們都看到今年出現的流感，

we're always a year behind and a dollar short

我們總是要慢上一年的時間並且在缺乏資金的情況下

when it comes to the right vaccine.

才等到有用的疫苗。

I think that can be changed

我認為這情形是可以改變的

by building combinatorial vaccines in advance.

透過預先製造混合疫苗。

Here's what the future may begin to look like

這是未來可能會呈現的情況

with changing, now, the evolutionary tree,

藉由改造基因, 現在的演化樹

speeding up evolution

會加速演化的速度

with synthetic bacteria, Archaea

這將會應用到人造細菌，古細菌

and, eventually, eukaryotes.

最終到真核生物上。

We're a ways away from improving people:

我們正在一條離改善人類生活越來越遠的路上。

our goal is just to make sure that we have a chance

我們的目標就是確保我們能有機會活到

to survive long enough to maybe do that. Thank you very much.

足夠長的時間或許就能做到這件事了。非常感謝大家。

(Applause)

（掌聲）