Craig Venter: A voyage of DNA, genes and the sea

翻译人员: lin qiang 校对人员: elyse lin

At the break, I was asked by several people

休息的时候，有几个人过来问我

about my comments about the aging debate.

对老龄化问题怎么看

And this will be my only comment on it.

我的唯一看法是

And that is, I understand

我认为

that optimists greatly outlive pessimists.

乐观主义者比悲观主义者活得久得多

(Laughter)

（笑声）

What I'm going to tell you about in my 18 minutes is

在这18分钟里我将告诉你们的是

how we're about to switch from reading the genetic code

我们是如何做到

to the first stages of beginning

从最初的阅读遗传编码

to write the code ourselves.

发展到我们自己开始编写遗传编码

It's only 10 years ago this month

仅仅十年之前的这个月

when we published the first sequence

我们发表了第一个

of a free-living organism,

来自自由活动生命体的基因序列

that of haemophilus influenzae.

即流感嗜血杆菌的序列

That took a genome project

由此我们将基因组项目完成的时间

from 13 years down to four months.

从13年降到4个月

We can now do that same genome project

现在，同样的基因组项目

in the order of

只需要

two to eight hours.

2到8个小时

So in the last decade, a large number of genomes have been added:

因此过去十年，我们完成了大量的基因组测序

most human pathogens,

大部分的人类病原体

a couple of plants,

几种植物

several insects and several mammals,

多种昆虫和哺乳动物

including the human genome.

包括人类基因组

Genomics at this stage of the thinking

约在十年前

from a little over 10 years ago

我们对基因组学发展的设想是

was, by the end of this year, we might have

到今年年底的时候

between three and five genomes sequenced;

我们或许能完成3到5个基因组的测序

it's on the order of several hundred.

而事实上已经完成了数百个

We just got a grant from the Gordon and Betty Moore Foundation

我们刚刚从戈登-贝蒂·摩尔基金会获得一笔资助

to sequence 130 genomes this year,

作为环境有机体项目的副项目

as a side project from environmental organisms.

我们将在今年完成130个基因组的测序

So the rate of reading the genetic code has changed.

阅读遗传编码的速率已然改变

But as we look, what's out there,

但我们看到，未来的路还很长

we've barely scratched the surface

我们仅仅探索了这个星球

on what is available on this planet.

表面上浅浅的一层

Most people don't realize it, because they're invisible,

大多数人没有意识到这些肉眼看不到的生物

but microbes make up about a half of the Earth's biomass,

微生物构成了地球约一半的生物量

whereas all animals only make up about

而所有的动物加起来

one one-thousandth of all the biomass.

也才占地球生物量的千分之一

And maybe it's something that people in Oxford don't do very often,

跑到海边喝上一口海水

but if you ever make it to the sea,

或许不是牛津人

and you swallow a mouthful of seawater,

经常做的事

keep in mind that each milliliter

但请记住每一毫升的海水里

has about a million bacteria

有大约一百万个的细菌

and on the order of 10 million viruses.

其中的病毒更是以千万计

Less than 5,000 microbial species

两年前只有不到五千种的微生物

have been characterized as of two years ago,

被鉴定归类

and so we decided to do something about it.

于是我们决定做些这方面的事情

And we started the Sorcerer II Expedition,

我们启动了巫师二号考察

where we were, as with great oceanographic expeditions,

和其他大型的海洋考察活动一样

trying to sample the ocean every 200 miles.

我们尝试每200英里采一次样

We started in Bermuda for our test project,

考察伊始，我们在百慕大进行了测试项目

then moved up to Halifax,

然后前往哈利法克斯

working down the U.S. East Coast,

接着到美国东海岸

the Caribbean Sea, the Panama Canal,

加勒比海、巴拿马运河

through to the Galapagos, then across the Pacific,

穿过加拉帕哥斯群岛，然后横跨太平洋

and we're in the process now of working our way

现在我们正在

across the Indian Ocean.

穿越印度洋的过程中

It's very tough duty; we're doing this on a sailing vessel,

工作很艰难，我们乘着一艘帆船

in part to help excite young people

某种程度上我们想通过它

about going into science.

激起年轻人投身科学的兴趣

The experiments are incredibly simple.

实验其实非常简单

We just take seawater and we filter it,

采集海水，过滤

and we collect different size organisms on different filters,

用不同的过滤器采集不同大小的生物

and then take their DNA back to our lab in Rockville,

然后把它们的DNA带回罗克韦尔的实验室

where we can sequence a hundred million letters

在那里我们可以每24小时

of the genetic code every 24 hours.

测完一亿字符的遗传编码

And with doing this,

通过这些

we've made some amazing discoveries.

我们已经有了一些惊人的发现

For example, it was thought that the visual pigments

比如我们眼睛里的视色素

that are in our eyes -- there was only one or two organisms

之前认为自然界中只有一到两种生物

in the environment that had these same pigments.

拥有和我们一样的视色素

It turns out, almost every species

但后来发现

in the upper parts of the ocean

在温暖海区的

in warm parts of the world

上层海水中

have these same photoreceptors,

几乎每个物种都拥有这类光受体

and use sunlight as the source of their energy

并利用阳光作为能量来源

and communication.

和交流工具

From one site, from one barrel of seawater,

仅仅一个采集点，从一桶水中

we discovered 1.3 million new genes

我们就能发现1300万个新基因

and as many as 50,000 new species.

相当于5万个新种

We've extended this to the air

借助来自斯隆基金会的资助

now with a grant from the Sloan Foundation.

我们已经将研究扩展到空气中

We're measuring how many viruses and bacteria

我们正在测算，在我们每天呼吸的空气中

all of us are breathing in and out every day,

漂浮着多少病毒和细菌

particularly on airplanes

特别是在飞机

or closed auditoriums.

和礼堂等封闭环境中

(Laughter)

（笑声）

We filter through some simple apparatuses;

我们通过一些简单的仪器进行过滤

we collect on the order of a billion microbes from just a day

在纽约市某栋建筑的顶上

filtering on top of a building in New York City.

仅用一天我们就过滤出数十亿计的微生物

And we're in the process of sequencing all that

目前

at the present time.

我们正在对它们进行测序

Just on the data collection side,

单纯从数据搜集方面

just where we are through the Galapagos,

仅仅在加拉帕戈斯群岛

we're finding that almost every 200 miles,

我们就发现几乎每200英里

we see tremendous diversity

我们都能从采集的样品中

in the samples in the ocean.

看到巨大的多样性

Some of these make logical sense,

不同的温度梯度

in terms of different temperature gradients.

或许可以部分解释这种多样性

So this is a satellite photograph

这是一张基于温度的卫星图片

based on temperatures -- red being warm,

红色表示温暖区域

blue being cold --

蓝色表示冷的区域

and we found there's a tremendous difference between

我们发现，在温暖海水中获得样品

the warm water samples and the cold water samples,

与冷海水中的样品

in terms of abundant species.

在物种的丰富程度上具有极大的差异

The other thing that surprised us quite a bit

另一个让我们感到惊奇的事情是

is these photoreceptors detect different wavelengths of light,

这些光受体能探测到不同波长的光

and we can predict that based on their amino acid sequence.

而我们能通过它们的氨基酸序列来推测这一过程

And these vary tremendously from region to region.

不同区域之间，它们（的机制）也差别巨大

Maybe not surprisingly,

或许不是很让人惊奇

in the deep ocean, where it's mostly blue,

在几乎是幽蓝的深海里

the photoreceptors tend to see blue light.

光受体倾向于“看”到蓝光

When there's a lot of chlorophyll around,

而当周围存在大量叶绿素的时候

they see a lot of green light.

它们则“看”到许多绿光

But they vary even more,

在向较极端的

possibly moving towards infrared and ultraviolet

红外和紫外波段移动时

in the extremes.

光受体的差别可能更大

Just to try and get an assessment

为了对我们采集的所有基因

of what our gene repertoire was,

进行评估

we assembled all the data --

我们汇总了所有数据

including all of ours thus far from the expedition,

包括到目前为止考察所得的所有数据

which represents more than half of all the gene data on the planet --

代表了地球上超过一半的基因数据

and it totaled around 29 million genes.

总共约2900万个基因

And we tried to put these into gene families

我们把这些基因放入基因家族中

to see what these discoveries are:

试图回答：

Are we just discovering new members of known families,

我们是发现了已知基因家族中的新成员

or are we discovering new families?

还是发现了新的基因家族？

And it turns out we have about 50,000

结果表明我们找到了大约5万个

major gene families,

主要的基因家族

but every new sample we take in the environment

但我们从环境中获得的每个新样品

adds in a linear fashion to these new families.

都只是对这些新基因家族的线性补充

So we're at the earliest stages of discovery

因此我们正处在发现地球生命

about basic genes,

及其组成部分

components and life on this planet.

和基因基础的最初阶段

When we look at the so-called evolutionary tree,

我们来看下所谓的进化树

we're up on the upper right-hand corner with the animals.

我们人类就在右上角，和动物们在一起

Of those roughly 29 million genes,

在动物界约2900万个基因中

we only have around 24,000

我们的基因组

in our genome.

才仅仅拥有24000个基因

And if you take all animals together,

如果把所有的动物算在一起

we probably share less than 30,000

我们与之分享着不到30000

and probably maybe a dozen

可能在1.2万或再多数千

or more thousand different gene families.

的不同的基因家族

I view that these genes are now

现在我不仅仅将这些基因视为

not only the design components of evolution.

进化的设计组件

And we think in a gene-centric view --

而且我们要从“基因中心观点”——

maybe going back to Richard Dawkins' ideas --

或许要追溯到理查德·道金斯的理论——

than in a genome-centric view,

而非“基因组中心观点”来思考

which are different constructs of these gene components.

它们对这些基因组件的构造方式是不同的

Synthetic DNA, the ability to synthesize DNA,

合成DNA，即人工合成DNA的能力

has changed at sort of the same pace

在过去的十年或二十年里

that DNA sequencing has

与DNA测序的能力

over the last decade or two,

在某种程度上是同步发展的

and is getting very rapid and very cheap.

而且都变得越来越快速和廉价

Our first thought about synthetic genomics came

有关合成基因组的想法

when we sequenced the second genome back in 1995,

是在1995年我们对第二个基因组

and that from mycoplasma genitalium.

即生殖道支原体测序的时候想到的

And we have really nice T-shirts that say,

我们还制作了相当不错的T恤

you know, "I heart my genitalium."

写着，“我爱惜我的生殖器”

This is actually just a microorganism.

这其实只不过是个微小的生物

But it has roughly 500 genes.

却拥有近500个基因

Haemophilus had 1,800 genes.

嗜血杆菌拥有1800个基因

And we simply asked the question,

我们提出疑问

if one species needs 800, another 500,

如果某物种需要800个基因，另一种需要500个

is there a smaller set of genes

是否能用一套更小的基因

that might comprise a minimal operating system?

组成一个微小的可运作生命系统

So we started doing transposon mutagenesis.

于是我们开始做转座子的突变发生

Transposons are just small pieces of DNA

转座子是随机插入遗传编码之中

that randomly insert in the genetic code.

的短的DNA片段

And if they insert in the middle of the gene, they disrupt its function.

如果转座子插入到基因中间，就会扰乱基因的功能

So we made a map of all the genes

因此我们找出

that could take transposon insertions

所有能够接受转座子插入的基因

and we called those "non-essential genes."

并为这些“非必需基因”制作了“地图”

But it turns out the environment is very critical for this,

但结果我们发现环境对此的影响非常关键

and you can only

我们只能根据

define an essential or non-essential gene

环境中确实存在的条件

based on exactly what's in the environment.

来定义必需和非必需基因

We also tried to take a more directly intellectual approach

我们还试图做一个更直观的研究

with the genomes of 13 related organisms,

对13个有亲缘关系的生物

and we tried to compare all of those, to see what they had in common.

我们试图比较它们的基因组，看它们是否有相同之处

And we got these overlapping circles. And we found only 173 genes

于是我们得到了这些重叠的圆圈，我们发现只有173个基因

common to all 13 organisms.

在这所有13种生物中是相同的

The pool expanded a little bit if we ignored

如果忽略掉一个细胞内寄生物的话

one intracellular parasite;

这个基因库还能扩展一点

it expanded even more

当我们审视核心的一组

when we looked at core sets of genes

约310个基因时

of around 310 or so.

基因库扩大更多

So we think that we can expand

因此我们认为可以从最少500个基因

or contract genomes, depending on your point of view here,

扩展或缩小

to maybe 300 to 400 genes

——取决你怎么看这个问题——

from the minimal of 500.

到约300到400个基因

The only way to prove these ideas

证明这些理论的唯一方法

was to construct an artificial chromosome with those genes in them,

是以这些基因人工构建一个染色体

and we had to do this in a cassette-based fashion.

而且我们必须用基于表达框的方式来达到这一目的

We found that synthesizing accurate DNA

我们发现大片段精确合成DNA

in large pieces was extremely difficult.

是非常非常困难的

Ham Smith and Clyde Hutchison, my colleagues on this,

我的同事汉姆·史密斯和克莱德·哈钦森

developed an exciting new method

发明了一个让人振奋的新方法

that allowed us to synthesize a 5,000-base pair virus

能让我们在短短两周时间内

in only a two-week period

合成一个拥有5000个碱基对的病毒

that was 100 percent accurate,

而且在基因序列和生物学特性上

in terms of its sequence and its biology.

都百分百精确

It was a quite exciting experiment -- when we just took the synthetic piece of DNA,

那是个相当让人兴奋的实验：我们仅仅把合成的DNA片段

injected it in the bacteria and all of a sudden,

注进细菌中，突然之间

that DNA started driving the production of the virus particles

DNA就开始引导病毒颗粒的合成

that turned around and then killed the bacteria.

而病毒反过来杀死了细菌

This was not the first synthetic virus --

这并非第一个合成的病毒

a polio virus had been made a year before --

一年前已有某种脊髓灰质炎病毒被制造了出来

but it was only one ten-thousandth as active

但这却是唯一达到百分之一活性的病毒

and it took three years to do.

耗时三年才合成成功

This is a cartoon of the structure of phi X 174.

这是Phi X-174结构的一个动画

This is a case where the software now builds its own hardware,

这是软件为自己构建硬件的活例子

and that's the notions that we have with biology.

也为我们的生物学提供了新想法

People immediately jump to concerns about biological warfare,

有人立即开始担心生物武器的威胁

and I had recent testimony before a Senate committee,

不久前我也在参议院委员会

and a special committee the U.S. government has set up

和另一个由美国政府成立

to review this area.

旨在评价这一领域的特殊委员会上作证

And I think it's important to keep reality in mind,

我认为最重要的是将事实牢记在心

versus what happens with people's imaginations.

而非人们对事情发生的想象

Basically, any virus that's been sequenced today --

基本上，任何现在已经被测序的病毒

that genome can be made.

其基因组都可以被合成

And people immediately freak out about things about Ebola or smallpox,

人们立马被埃博拉病毒或天花病毒之类等吓坏了

but the DNA from this organism is not infective.

但从这些生物体中提取的DNA并不具有感染力

So even if somebody made the smallpox genome,

因此即使有人制成了天花病毒基因组

that DNA itself would not cause infections.

其DNA本身并不会引发感染

The real concern that security departments have

安全部门真正需要担心的是

is designer viruses.

“设计者病毒”

And there's only two countries, the U.S. and the former Soviet Union,

只有两个国家，美国和前苏联

that had major efforts

曾经花大力气

on trying to create biological warfare agents.

致力于生物武器的研制

If that research is truly discontinued,

如果这些研究真的已经终止

there should be very little activity

那么在未来

on the know-how to make designer viruses in the future.

人为制造出设计者病毒的几率微乎其微

I think single-cell organisms are possible within two years.

我想两年内制造出单细胞生物是可能的

And possibly eukaryotic cells,

而真核细胞

those that we have,

我们自己拥有的这种细胞

are possible within a decade.

也可能在十年内制造出来

So we're now making several dozen different constructs,

我们可以区分开进入这个人工基因组的

because we can vary the cassettes and the genes

不同表达框和不同基因

that go into this artificial chromosome.

使得我们能构建数十种不同的结构

The key is, how do you put all of the others?

关键是，如何把所有其他的（基因）放进来？

We start with these fragments,

我们从这些片段开始

and then we have a homologous recombination system

然后通过一个同源重组系统

that reassembles those into a chromosome.

将其组合到染色体中

This is derived from an organism, deinococcus radiodurans,

这来自一种名为耐辐射奇异球菌的生物

that can take three million rads of radiation and not be killed.

能在三百万拉德的辐射剂量下保持活力

It reassembles its genome after this radiation burst

在暴露辐射约12到24小时

in about 12 to 24 hours,

其染色体几乎完全破碎的情况下

after its chromosomes are literally blown apart.

它还能将自身的染色体重新组装起来

This organism is ubiquitous on the planet,

这种生物在地球上几乎无处不在

and exists perhaps now

甚至由于人类的活动

in outer space due to all our travel there.

它们还可能在外太空活动

This is a glass beaker after

这是玻璃烧杯

about half a million rads of radiation.

在约50万拉德辐射下的情形

The glass started to burn and crack,

玻璃开始燃烧，爆裂

while the microbes sitting in the bottom

而位于底部的微生物

just got happier and happier.

则似乎越来越开心

Here's an actual picture of what happens:

这是实际的情形

the top of this shows the genome

上面是经过170万拉德辐射

after 1.7 million rads of radiation.

之后的染色体

The chromosome is literally blown apart.

几乎已经支离破碎

And here's that same DNA automatically reassembled

下面是24小时之后

24 hours later.

同样的DNA自动重组的结果

It's truly stunning that these organisms can do that,

这些生物能做到的真是叹为观止。

and we probably have thousands,

如果不是数以万计的话

if not tens of thousands, of different species

也许我们还能找到数以千计

on this planet that are capable of doing that.

的物种也同样能够做到

After these genomes are synthesized,

这些基因组合成之后

the first step is just transplanting them

第一步就是将它们

into a cell without a genome.

移植到另一个没有基因组的细胞中

So we think synthetic cells are going to have tremendous potential,

因此我们认为合成细胞将具有巨大的前景

not only for understanding the basis of biology

不仅仅在生物学基础的理解上

but for hopefully environmental and society issues.

而且很可能帮我们应对环境和社会问题

For example, from the third organism we sequenced,

例如，从我们测序的第三种生物

Methanococcus jannaschii -- it lives in boiling water temperatures;

詹氏甲烷球菌，生活在相当于水沸点的高温中

its energy source is hydrogen

以氢作为能量来源

and all its carbon comes from CO2 it captures back from the environment.

并依靠捕获环境中的二氧化碳为自己提供所需的碳

So we know lots of different pathways,

由此可知，通过大量不同的途径

thousands of different organisms now

数以千计的生物

that live off of CO2,

能够捕获

and can capture that back.

并依赖二氧化碳生存

So instead of using carbon from oil

因此我们可以通过

for synthetic processes,

捕获大气中的碳

we have the chance of using carbon

制造生物高聚物

and capturing it back from the atmosphere,

或其他产品

converting that into biopolymers

来替代从石油中

or other products.

工业合成的碳制品

We have one organism that lives off of carbon monoxide,

有种依赖一氧化碳的生物

and we use as a reducing power

我们利用其还原能力

to split water to produce hydrogen and oxygen.

使水分子破裂，制造出氢和氧

Also, there's numerous pathways

同样，还有许多途径

that can be engineered metabolizing methane.

能够用来转化甲烷

And DuPont has a major program with Statoil in Norway

杜邦公司和挪威石油公司有一大型项目

to capture and convert the methane

就是把挪威油气田中的甲烷

from the gas fields there into useful products.

转化为有用的产品

Within a short while, I think there's going to be a new field

我突然想到，将有一个新的领域

called "Combinatorial Genomics,"

“组合基因组学”很快就要诞生

because with these new synthesis capabilities,

因为有了这些新的合成方法

these vast gene array repertoires

有了这么庞大的基因序列

and the homologous recombination,

和同源重组

we think we can design a robot to make

我们可以设计出一个

maybe a million different chromosomes a day.

能够每天生产近百万个染色体的机器人

And therefore, as with all biology,

因此，所有的生物学特征

you get selection through screening,

都能通过屏幕来选择

whether you're screening for hydrogen production,

无论是制造氢

or chemical production, or just viability.

化学合成，或者仅仅是生存能力

To understand the role of these genes

理解这些基因的功能

is going to be well within reach.

将变得触手可及

We're trying to modify photosynthesis

我们正尝试改进光合作用

to produce hydrogen directly from sunlight.

以直接在阳光下制造出氢

Photosynthesis is modulated by oxygen,

光合作用受氧调节

and we have an oxygen-insensitive hydrogenase

而我们使用的对氧不敏感的氢化酶

that we think will totally change this process.

将完全改变这一过程

We're also combining cellulases,

我们还整合了多种纤维素酶

the enzymes that break down complex sugars into simple sugars

这些酶可以把复杂的糖类分解为简单的糖类

and fermentation in the same cell

并在同一个细胞内发酵

for producing ethanol.

产生酒精

Pharmaceutical production is already under way

在一些大型的实验室里

in major laboratories

已经开始利用微生物

using microbes.

进行药品生产

The chemistry from compounds in the environment

环境中化合物的化学

is orders of magnitude more complex

比我们最好的化学家制造出来的化合物

than our best chemists can produce.

还要复杂很多

I think future engineered species

也许未来的工程物种将成为

could be the source of food,

我们的食物来源

hopefully a source of energy,

能量来源

environmental remediation

环境补救手段

and perhaps

甚至

replacing the petrochemical industry.

取代石化行业

Let me just close with ethical and policy studies.

最后让我以道德和政策上的研究结束吧

We delayed the start of our experiments in 1999

我们推迟了1999年开始的实验

until we completed a year-and-a-half bioethical review

直到对是否应该尝试制造人工物种这一问题进行了一年半的生物伦理学讨论后

as to whether we should try and make an artificial species.

实验才继续进行

Every major religion participated in this.

每个主要宗教都参与其中

It was actually a very strange study,

真是一项奇怪的研究

because the various religious leaders were using their scriptures as law books,

因为许多宗教领袖都以他们的教义、经文作为法律

and they couldn't find anything in them prohibiting making life,

而且不能从中找出禁止制造生命的条文

so it must be OK. The only ultimate concerns

所以这应该没什么问题

were biological warfare aspects of this,

最根本的担忧来自生物武器方面

but gave us the go ahead to start these experiments

但只有开始进行这些实验之后

for the reasons we were doing them.

我们才能找出从事这一切的原因

Right now the Sloan Foundation has just funded

目前斯隆基金会已经资助了

a multi-institutional study on this,

一个相关的多机构参与的研究

to work out what the risk and benefits to society are,

以确定这些实验给社会带来的风险和益处

and the rules that scientific teams such as my own

同时也为像我们这样的科学团队

should be using in this area,

在这一领域开展研究制定规则

and we're trying to set good examples as we go forward.

在前进的同时我们也努力成为一个良好的榜样

These are complex issues.

有许多复杂的议题

Except for the threat of bio-terrorism,

除了生物恐怖主义

they're very simple issues in terms of,

它们其实都很简单：

can we design things to produce clean energy,

我们能否设计出生产清洁能源的工具

perhaps revolutionizing

通过各种不同的简单步骤

what developing countries can do

或能彻底改变

and provide through various simple processes.

发展中国家的能源生产模式

Thank you very much.

非常感谢