Craig Venter unveils "synthetic life"

譯者: Wenjer Leuschel 審譯者: Fumin Chiu

We're here today to announce

我們今天在此宣佈

the first synthetic cell,

第一個合成細胞製作成功

a cell made by

這細胞我們先以數碼的方式

starting with the digital code in the computer,

在電腦裡建構

building the chromosome

再從四瓶化學物質

from four bottles of chemicals,

築出染色體

assembling that chromosome in yeast,

並在酵母中組合該細胞的染色體

transplanting it into

然後再把它移植到

a recipient bacterial cell

接收的細菌細胞裡

and transforming that cell

使那個細胞轉化

into a new bacterial species.

成為一個新的菌種

So this is the first self-replicating species

於是成為我們這個地球上

that we've had on the planet

第一個誕生於電腦

whose parent is a computer.

而能自我複製的物種

It also is the first species

它也將是第一個

to have its own website

把自己的網址寫入

encoded in its genetic code.

自己的基因密碼裡的物種

But we'll talk more about

不過我們稍後

the watermarks in a minute.

再多談浮水印之事

This is a project that had its inception

這個研究專案肇始於

15 years ago

15年前

when our team then --

當時我們的研究團隊－

we called the institute TIGR --

稱為TIGR研究所－

was involved in sequencing

進行了有史以來首次的

the first two genomes in history.

兩個基因組排序工作

We did Haemophilus influenzae

我們先為流感嗜血桿菌

and then the smallest genome of a self-replicating organism,

然後又為能自行複製的生物體

that of Mycoplasma genitalium.

生殖支原體的最小基因組做了排序

And as soon as

我們一旦有了

we had these two sequences

這兩個排序

we thought, if this is supposed to be the smallest genome

我們想, 如果這被認為是能自行複製的

of a self-replicating species,

物種的最小基因組

could there be even a smaller genome?

那麼還有更小的嗎？

Could we understand the basis of cellular life

我們能在基因的層面上理解

at the genetic level?

細胞生命的基礎嗎？

It's been a 15-year quest

這一問就是15年

just to get to the starting point now

今天我們才剛走到開始

to be able to answer those questions,

可以回答那些問題的地步

because it's very difficult to eliminate

由於很難消除細胞裡的

multiple genes from a cell.

多重基因

You can only do them one at a time.

只能一次消除一個

We decided early on

所以我們很早就決定

that we had to take a synthetic route,

即使以前沒有人做過

even though nobody had been there before,

我們必須採取合成的辦法

to see if we could synthesize

看看我們能否合成

a bacterial chromosome

一個細菌的染色體

so we could actually vary the gene content

由此我們改變了基因內容

to understand the essential genes for life.

以便理解生命的基本基因

That started our 15-year quest

於是開始了我們15年的探索

to get here.

終於達到今天的地步

But before we did the first experiments,

開始進行首先的實驗之前

we actually asked

我們確實先向當時在賓州大學的

Art Caplan's team at the University of Pennsylvania

Art Caplan研究團隊尋求

to undertake a review

進行評估審查

of what the risks, the challenges,

以確定在實驗室裡創造

the ethics around creating new

新物種的風險、挑戰

species in the laboratory were

和道德方面的問題

because it hadn't been done before.

因為這是史無前例的

They spent about two years

他們花了大約兩年時間

reviewing that independently

獨立完成評審

and published their results in Science in 1999.

將其結果發表於1999年《科學雜誌》

Ham and I took two years off

當時我和Ham離開兩年

as a side project to sequence the human genome,

進行人類基因組排序的另一個研究專案

but as soon as that was done

完成工作後

we got back to the task at hand.

我們立即回到這個工作

In 2002, we started

2002年, 我們開始

a new institute,

一個新的研究所

the Institute for Biological Energy Alternatives,

生物能源替代方案研究所

where we set out two goals:

我們設定了兩個目標

One, to understand

其一是要理解

the impact of our technology on the environment,

我們的科技對環境的影響並確定

and how to understand the environment better,

如何更妥善理解環境問題

and two, to start down this process

其二是開始建構

of making synthetic life

製作合成生命的過程

to understand basic life.

以便理解基礎生命

In 2003,

在2003年

we published our first success.

我們發表了初步的成果

So Ham Smith and Clyde Hutchison

Ham Smith和Clyde Hutchison

developed some new methods

開發了一些新的方法

for making error-free DNA

用來小規模製作

at a small level.

無差錯的DNA

Our first task was

當時的第一個工作是

a 5,000-letter code bacteriophage,

一個5000字母代碼的噬菌體

a virus that attacks only E. coli.

是一種只會攻擊大腸桿菌的病毒

So that was

那就是編號

the phage phi X 174,

ΦX174的噬菌體

which was chosen for historical reasons.

選擇它有歷史的緣由

It was the first DNA phage,

它是第一個真正受到完整

DNA virus, DNA genome

排序的DNA噬菌體、DNA病毒、

that was actually sequenced.

DNA基因組

So once we realized

那麼我們一旦明白

that we could make 5,000-base pair

我們能製作出5000個在

viral-sized pieces,

病毒般大小內的核酸鹼基對

we thought, we at least have the means

我們想，我們至少有了方法

then to try and make serially lots of these pieces

進一步嘗試批量製作這些配對

to be able to eventually assemble them together

以便在最後把它們組合起來

to make this mega base chromosome.

製作成這個兆基的染色體

So, substantially larger than

這個進展基本上甚至

we even thought we would go initially.

比我們原先所想要組合的還大出許多

There were several steps to this. There were two sides:

達到這個地步有幾個步驟，分兩方面來說

We had to solve the chemistry

我們必須在化學方面解決

for making large DNA molecules,

製作大型DNA分子的問題

and we had to solve the biological side

另外在生物學方面我們必須解決

of how, if we had this new chemical entity,

有了這個新的化學實體之後

how would we boot it up, activate it

如何在一個接收細胞裡

in a recipient cell.

將它啟動、將它活化的問題

We had two teams working in parallel:

因此我們有兩個團隊併列進行

one team on the chemistry,

一個團隊處理化學的問題

and the other on trying to

另一個團隊嘗試

be able to transplant

如何能夠移植

entire chromosomes

整個染色體

to get new cells.

以獲得新的細胞

When we started this out, we thought the synthesis would be the biggest problem,

開始時我們以為最大的問題會在於合成

which is why we chose the smallest genome.

那是我們當時選擇最小的基因組的原因

And some of you have noticed that we switched from the smallest genome

各位有人注意到我們改用相當大的基因組

to a much larger one.

而沒有採用最小的

And we can walk through the reasons for that,

我們可以略過這個改動的原因

but basically the small cell

不過基本上, 採用小型的細胞

took on the order of

要得到結果

one to two months to get results from,

需要花費一到兩個月時間

whereas the larger, faster-growing cell

但若採用較大、成長較快的細胞

takes only two days.

只需要兩天

So there's only so many cycles we could go through

因此我們在一年內

in a year at six weeks per cycle.

以六週為一期，只能進行那麼多週期

And you should know that basically

而且各位應該知道

99, probably 99 percent plus

基本上我們的實驗有99%

of our experiments failed.

甚至可能99%以上會是失敗的

So this was a debugging,

因此整個工作從一開始

problem-solving scenario from the beginning

就是糾錯, 解決問題的戲碼

because there was no recipe

因為當時還沒有

of how to get there.

達到成功的訣竅

So, one of the most important publications we had

我們最重要的發表之一

was in 2007.

是在2007年

Carole Lartigue led the effort

Carole Lartigue主持的那個研究

to actually transplant a bacterial chromosome

說明如何將細菌染色體

from one bacteria to another.

從一個細菌移植到另一個

I think philosophically, that was one of the most important papers

哲學意義上，我認為那是我們做過的研究中

that we've ever done

最為重要的報告之一

because it showed how dynamic life was.

因為該報告顯示了生命具有多大的動能

And we knew, once that worked,

我們知道, 只要這方法奏效

that we actually had a chance

那麼我們很有可能

if we could make the synthetic chromosomes

做到讓合成的染色體

to do the same with those.

同樣能夠移植到細菌細胞裡

We didn't know that it was going to take us

只是當時還不知道還要

several years more to get there.

多少年才能做到那個地步

In 2008,

2008年

we reported the complete synthesis

我們發表了完成合成

of the Mycoplasma genitalium genome,

生殖支原體基因組的報告

a little over 500,000 letters of genetic code,

比500,000字母稍多一點的基因密碼

but we have not yet succeeded in booting up that chromosome.

但是我們還未成功地啟動該染色體

We think in part, because of its slow growth

我們認為部分原因是由於成長緩慢

and, in part,

另外部分原因是

cells have all kinds of unique defense mechanisms

細胞都具有各種特殊的防衛機制

to keep these events from happening.

使得啟動植入困難

It turned out the cell that we were trying to transplant into

我們發現我們嘗試植入的細胞

had a nuclease, an enzyme that chews up DNA on its surface,

有一種會在其表面啃蝕DNA的核酸酵素

and was happy to eat

吃起我們給它的合成DNA

the synthetic DNA that we gave it

特別痛快

and never got transplantations.

因此移植一直沒有成功

But at the time, that was the largest

不過那是我們當時

molecule of a defined structure

所知做過的分子結構

that had been made.

最大的一個

And so both sides were progressing,

因此兩方面當時都在進展之中

but part of the synthesis

但合成有部分必須完成

had to be accomplished or was able to be accomplished

或說仍須完成

using yeast, putting the fragments in yeast

使用酵母－把片段放入酵母中

and yeast would assemble these for us.

酵母就會幫我們組合

It's an amazing step forward,

這是令人驚訝的進步

but we had a problem because now we had

但是我們卻有了新的問題

the bacterial chromosomes growing in yeast.

因為我們的細菌染色體現在是在酵母中成長的

So in addition to doing the transplant,

因此除了要進行移植之外

we had to find out how to get a bacterial chromosome

我們還得找出一個方法從真核酵母中

out of the eukaryotic yeast

取出細菌染色體

into a form where we could transplant it

而且要確保取出後

into a recipient cell.

能被移植到一個接收細胞裡

So our team developed new techniques

因此我們的研究團隊開發了一個新技術

for actually growing, cloning

用來在酵素中促長

entire bacterial chromosomes in yeast.

並複製整著細菌染色體

So we took the same mycoides genome

因此我們採用相同於Carole原本移植的

that Carole had initially transplanted,

柔膜菌支原體基因組

and we grew that in yeast

作為人造染色體

as an artificial chromosome.

讓它在酵母中成長

And we thought this would be a great test bed

我們當時認為, 這會是學習如何從酵母中

for learning how to get chromosomes out of yeast

取出染色體並做移植的

and transplant them.

很好的試驗床

When we did these experiments, though,

但當我們做實驗時

we could get the chromosome out of yeast

我們雖能從酵母中取出染色體

but it wouldn't transplant and boot up a cell.

但無法移植並啟動細胞

That little issue took the team two years to solve.

這麼個小問題花了研究團隊兩年才解決

It turns out, the DNA in the bacterial cell

結果發現在細菌細胞裡的DNA

was actually methylated,

原來是經過甲基化的

and the methylation protects it from the restriction enzyme,

而甲基化保護它不接受限制酶

from digesting the DNA.

不能消化DNA

So what we found is if we took the chromosome

因此我們發現, 如果從酵母

out of yeast and methylated it,

取出染色體並將它甲基化

we could then transplant it.

我們就可以移植了

Further advances came

當研究團隊

when the team removed the restriction enzyme genes

將限制酶基因從山羊支原體移除時

from the recipient capricolum cell.

我們便更進了一步

And once we had done that, now we can take

一旦達到這一步

naked DNA out of yeast and transplant it.

我們便能從酵母中取出裸露的DNA進行移植

So last fall

於是去年秋天

when we published the results of that work in Science,

我們在《科學雜誌》發表該研究成果時

we all became overconfident

我們都變得過於自信

and were sure we were only

確信我們只須

a few weeks away

再幾個星期的時間

from being able to now boot up

就能夠啟動

a chromosome out of yeast.

從酵母中取出的染色體

Because of the problems with

由於約一年半前

Mycoplasma genitalium and its slow growth

有過生殖支原體以及其

about a year and a half ago,

成長緩慢的問題

we decided to synthesize

我們決定合成

the much larger chromosome, the mycoides chromosome,

較大的柔膜菌支原體染色體

knowing that we had the biology worked out on that

因為我們在生物學方面已經解決了

for transplantation.

此等染色體的移植問題

And Dan led the team for the synthesis

當時Dan帶領合成這個

of this over one-million-base pair chromosome.

超過百萬核酸鹼基對染色體的研究團隊

But it turned out it wasn't going to be as simple in the end,

但終究發現沒有那麼簡單

and it set us back three months

這讓我們損失三個月時間

because we had one error

因為我們在那個超過

out of over a million base pairs in that sequence.

百萬核酸鹼基對排序中有一個錯誤

So the team developed new debugging software,

於是研究團隊開發了新的糾錯軟體

where we could test each synthetic fragment

用來測試每個合成的片段

to see if it would grow in a background

查看它能否

of wild type DNA.

在雜型的DNA背景下成長

And we found that 10 out of the 11

結果發現我們合成的每十萬個核酸鹼基對裡

100,000-base pair pieces we synthesized

11個之中有10個

were completely accurate

是完全精確的

and compatible with

而且也與

a life-forming sequence.

形成生命的排序相容

We narrowed it down to one fragment;

我們縮小問題的範圍至那一個片段

we sequenced it

為那一個片段作基因排序

and found just one base pair had been deleted

發現只有一個重要基因的

in an essential gene.

一個核酸鹼基對被消除了

So accuracy is essential.

因此精確是至關緊要的

There's parts of the genome

有些基因組的部分

where it cannot tolerate even a single error,

一點小錯都不能容忍

and then there's parts of the genome

還有些基因組的部分

where we can put in large blocks of DNA,

我們可以放入大塊的DNA

as we did with the watermarks,

我們就是這麼放入浮水印的

and it can tolerate all kinds of errors.

這些部分很能容忍各種錯誤

So it took about three months to find that error

於是花費了大約三個月時間找到那個錯誤

and repair it.

並予修正

And then early one morning, at 6 a.m.

然後有一天早上六點鐘

we got a text from Dan

我們收到Dan發來簡訊

saying that, now, the first blue colonies existed.

說是第一個藍色菌落已經形成了

So, it's been a long route to get here:

那麼，達到今天的地步是一條很長的路－

15 years from the beginning.

從開始到現在整整15年

We felt

我們覺得

one of the tenets of this field

這個領域的信條之一是

was to make absolutely certain

要做到完全確定

we could distinguish synthetic DNA

我們要能切實分辨合成DNA

from natural DNA.

和自然DNA的區別

Early on, when you're working in a new area of science,

在科學的一個新領域中進行研究工作時

you have to think about all the pitfalls

很早就要想到所有可能的陷阱

and things that could lead you

以及會誤導你相信有了成果

to believe that you had done something when you hadn't,

但實際並沒有成就什麼的情況

and, even worse, leading others to believe it.

更糟糕的是也誤導了別人相信

So, we thought the worst problem would be

因此我們認為最糟糕的

a single molecule contamination

問題會是由於原本的染色體

of the native chromosome,

有某個單分子受到污染

leading us to believe that we actually had

誤導我們相信我們真的創造出

created a synthetic cell,

一個合成的細胞

when it would have been just a contaminant.

而可能只是一個污染的產物

So early on, we developed the notion

因此我們很早就有了

of putting in watermarks in the DNA

要在DNA裡放入浮水印的想法

to absolutely make clear

以弄清楚那個DNA

that the DNA was synthetic.

絕對毫無疑問是合成的

And the first chromosome we built

我們建構的第一個染色體

in 2008 --

在2008年

the 500,000-base pair one --

那個有五十萬個核酸鹼基對的

we simply assigned

染色體內, 我們放入了

the names of the authors of the chromosome

作者們的姓名

into the genetic code,

在其基因密碼中,

but it was using just amino acid

但當時只採用胺基酸

single letter translations,

的單字母代碼,

which leaves out certain letters of the alphabet.

這個系統省略了字母系統裡的某些字母

So the team actually developed a new code

因此研究團隊開發了一套新密碼

within the code within the code.

那是在密碼裡的密碼裡的密碼

So it's a new code

那麼就是一種新密碼

for interpreting and writing messages in DNA.

用來解讀和書寫在DNA裡的信息

Now, mathematicians have been hiding and writing

是的，數學家長久以來已經在進行著

messages in the genetic code for a long time,

隱藏和書寫基因密碼的工作

but it's clear they were mathematicians and not biologists

但清楚的是他們是數學家不是生物學家

because, if you write long messages

因為如果你使用數學家開發的密碼

with the code that the mathematicians developed,

書寫長的信息

it would more than likely lead to

其結果很可能導致

new proteins being synthesized

新蛋白質的合成

with unknown functions.

而其功能卻不清楚

So the code that Mike Montague and the team developed

那麼Mike Montague和他的團隊開發的密碼

actually puts frequent stop codons,

確實放入常見的停止密碼子

so it's a different alphabet

因此這是一套不同的字母系統

but allows us to use

但卻讓我們能使用

the entire English alphabet

整個英文字母系統裡的字母

with punctuation and numbers.

包含標點和數字

So, there are four major watermarks

於是有四種主要的浮水印

all over 1,000 base pairs of genetic code.

散布在上千個基因密碼的核酸鹼基對裡

The first one actually contains within it

實際包含在內的第一種

this code for interpreting

是用來解讀其它

the rest of the genetic code.

基因密碼的密碼

So in the remaining information,

因此在其餘的訊息中

in the watermarks,

在浮水印裡

contain the names of, I think it's

包含了－我想沒錯－是

46 different authors

46位不同的作者

and key contributors

以及主要的貢獻者

to getting the project to this stage.

他們推動研究專案到達這個地步

And we also built in

而且我們也植入

a website address

一個網站的位址

so that if somebody decodes the code

因此如果有人解開

within the code within the code,

密碼裡的密碼裡的密碼

they can send an email to that address.

就可以傳送一封電子郵件到那個位址

So it's clearly distinguishable

因此可以清楚地分辨出

from any other species,

它與其它物種的區別

having 46 names in it,

因為裡頭有46個姓名

its own web address.

還有它自己的網址

And we added three quotations,

我們還添加了三句引文

because with the first genome

因為做出第一個基因組時

we were criticized for not trying to say something more profound

我們被批評沒有嘗試說些有點深度的言語

than just signing the work.

只為研究工作簽了名

So we won't give the rest of the code,

那麼不多說其它的密碼

but we will give the three quotations.

我們只說那三句引文

The first is,

第一句是

"To live, to err,

「活著、犯錯、

to fall, to triumph

跌跤、獲勝，

and to recreate life out of life."

還要從生命中創造生命。」

It's a James Joyce quote.

這是引自James Joyce的言語

The second quotation is, "See things not as they are,

第二句引文是「見事物勿僅見其然，

but as they might be."

亦當見其或可以然。」

It's a quote from the "American Prometheus"

這是引自談論Robert Oppenheimer的

book on Robert Oppenheimer.

《美國的普羅修斯》的言語

And the last one is a Richard Feynman quote:

最後一句是Richard Feynman的言語

"What I cannot build,

「若是我無法建構，

I cannot understand."

即因我不全然理解。」

So, because this is as much a philosophical advance

那麼由於這是在科學技術上的進步

as a technical advance in science,

也同樣是在哲學上的進步

we tried to deal with both the philosophical

我們試圖處理技術方面的事

and the technical side.

同時也處理哲學方面的事

The last thing I want to say before turning it over to questions

轉到提問之前

is that the extensive work

我最後要說的是

that we've done --

我們大費周章

asking for ethical review,

請求道德方面的評審

pushing the envelope

在那方面推到極限

on that side as well as the technical side --

也在技術方面推到極限

this has been broadly discussed in the scientific community,

這在科學社群裡已經受到廣泛討論

in the policy community

在政策制訂社群裡

and at the highest levels of the federal government.

還有在聯邦政府的最高層也討論

Even with this announcement,

甚至這次的宣佈－

as we did in 2003 --

如同2003年那次－

that work was funded by the Department of Energy,

那個研究是由能源部所資助的－

so the work was reviewed

那麼我們的研究工作

at the level of the White House,

受到白宮層級的評審

trying to decide whether to classify the work or publish it.

以決定此研究是否列為保密或得以發表

And they came down on the side of open publication,

他們最後的決定是站在公開發表這邊

which is the right approach --

這是正確的做法

we've briefed the White House,

我們向白宮做過了報告

we've briefed members of Congress,

我們也向國會做了報告

we've tried to take and push

在科學進步的同時

the policy issues

我們嘗試了

in parallel with the scientific advances.

研擬和推動政策討論

So with that, I would like

這些都做過了

to open it first to the floor for questions.

所以我們現在可以開始接受提問

Yes, in the back.

好的，後面那一位請提問

Reporter: Could you explain, in layman's terms,

記者：可否請您用簡單的語言

how significant a breakthrough this is please?

解釋這個突破到底有多重大？

Craig Venter: Can we explain how significant this is?

CV：可否解釋這個突破有多重大？

I'm not sure we're the ones that should be explaining how significant it is.

我不確定我們有資格做這種解釋

It's significant to us.

對我們而言確是重大突破

Perhaps it's a giant philosophical change

也許在哲學上這是巨大的改變

in how we view life.

它改變我們看待生命的方式

We actually view it as a baby step in terms of,

我們其實把這當作嬰兒學步看待

it's taken us 15 years to be able

因為我們花費15年

to do the experiment

才得以做出

we wanted to do 15 years ago

這15年前想做出

on understanding life at its basic level.

在生命基礎上理解生命的實驗

But we actually believe

不過我們確實相信

this is going to be a very powerful set of tools

這將會是一套非常強大的工具

and we're already starting

我們在許多研究上

in numerous avenues

已經實際開始

to use this tool.

應用這些工具

We have, at the Institute,

我們研究所現在

ongoing funding now from NIH

正在向NIH集資準備

in a program with Novartis

與諾華合作進行一個方案

to try and use these new

以便測試並使用這些

synthetic DNA tools

新的合成DNA的工具

to perhaps make the flu vaccine

或許用來製作明年

that you might get next year.

可能就會用到的流感疫苗

Because instead of taking weeks to months to make these,

因為以往需要花費好幾個星期或好幾個月

Dan's team can now make these

Dan的研究團隊現在可以

in less than 24 hours.

在24小時內完成這些工作

So when you see how long it took to get an H1N1 vaccine out,

那麼想一想H1N1疫苗花費了多少時間

we think we can shorten that process

我們認為我們可以

quite substantially.

大幅縮短那個過程

In the vaccine area,

在疫苗的領域裡

Synthetic Genomics and the Institute

「合成基因組學」和研究所

are forming a new vaccine company

正在組織一個新的疫苗公司

because we think these tools can affect vaccines

因為我們認為這些工具對於至今可能

to diseases that haven't been possible to date,

還無法控制的病毒變體快速演化的

things where the viruses rapidly evolve,

疾病之疫苗－例如鼻病毒－

such with rhinovirus.

可能會有所影響

Wouldn't it be nice to have something that actually blocked common colds?

要是能有可以阻絕一般感冒的東西，不是很好嗎？

Or, more importantly, HIV,

或更重要的是HIV

where the virus evolves so quickly

那種病毒變體演化之快

the vaccines that are made today

今天製作的疫苗

can't keep up

根本跟不上

with those evolutionary changes.

那些病毒的演化改變

Also, at Synthetic Genomics,

還有，在「合成基因組學」

we've been working

我們一直進行著重大

on major environmental issues.

環境問題的研究工作

I think this latest oil spill in the Gulf

我想最進的海灣漏油事件

is a reminder.

正是一個提醒我們的話題

We can't see CO2 --

我們看不見二氧化碳

we depend on scientific measurements for it

我們依靠科學的測量

and we see the beginning results

我們才剛開始看到

of having too much of it --

二氧化碳過多的結果

but we can see pre-CO2 now

卻看到二氧化碳的前身

floating on the waters

現在就浮動在水面上

and contaminating the beaches in the Gulf.

污染著海灣的沙灘

We need some alternatives

我們必須找到一些

for oil.

替代石油的方案

We have a program with Exxon Mobile

我們和埃克森美孚有個計畫

to try and develop new strains of algae

嘗試並開發能夠

that can efficiently capture carbon dioxide

從大氣中或從高濃度的來源裡

from the atmosphere or from concentrated sources,

有效捕捉二氧化碳的新種海藻

make new hydrocarbons that can go into their refineries

製作新的碳水化合物用於他們的煉油廠

to make normal gasoline

用以製造不產生二氧化碳的

and diesel fuel out of CO2.

正常汽油和柴油燃料

Those are just a couple of the approaches

這些只是舉例說明

and directions that we're taking.

我們的做法和走向

(Applause)

（掌聲）