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

譯者: Boyang Zhu 審譯者: Shelley Krishna Tsang

At the break, I was asked by several people

演講開始之前，我遇到幾個人

about my comments about the aging debate.

問我對於老化議題的看法

And this will be my only comment on it.

關於這個問題我唯一的

And that is, I understand

看法就是

that optimists greatly outlive pessimists.

樂觀的人比悲觀者要活的久的多

(Laughter)

(笑聲)

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

在這18分鐘內我將告訴各位的是

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

我們如何從破解基因編碼

to the first stages of beginning

進步到可以開始

to write the code ourselves.

自己編寫基因編碼

It's only 10 years ago this month

僅僅是10年前的同一個月

when we published the first sequence

我們公佈了第一組取自一種

of a free-living organism,

非寄生有機體的基因序列

that of haemophilus influenzae.

叫做嗜血桿菌

That took a genome project

它將原本耗時13年的

from 13 years down to four months.

基因計畫縮短到4個月

We can now do that same genome project

我們現在只需要

in the order of

2到8個小時

two to eight hours.

就能完成相同的計畫

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

因此過去10年間，我們研究了許多基因組

most human pathogens,

大部分是人類病源體

a couple of plants,

幾種植物的基因組

several insects and several mammals,

以及一些昆蟲和哺乳類的基因組

including the human genome.

當然也包括人類

Genomics at this stage of the thinking

回顧10多年前剛剛起步的

from a little over 10 years ago

基因組學科進行

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

到今年年底，我們可能已經完成了

between three and five genomes sequenced;

三到五組基因組的測序

it's on the order of several hundred.

但這只是約幾百組中的一小部分

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

我們最近接受了「戈登與貝蒂‧摩爾基金」資助

to sequence 130 genomes this year,

作為對環境有機體研究的附屬計畫

as a side project from environmental organisms.

在今年進行130組基因組的測序。

So the rate of reading the genetic code has changed.

對基因編碼的讀取速度已經發生變化。

But as we look, what's out there,

但是放眼世界，

we've barely scratched the surface

我們對地球上的萬物

on what is available on this planet.

仍然知之甚少。

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

大部份人很難意識到是因為它們是肉眼所看不見的，

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

但微生物佔據了地球上生物總量的一半。

whereas all animals only make up about

所有的動物只在生物總量

one one-thousandth of all the biomass.

佔了大約千分之一。

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

可能住在牛津的人們通常不會這樣做。

but if you ever make it to the sea,

但是你要是去海邊，

and you swallow a mouthful of seawater,

吞一口海水，

keep in mind that each milliliter

那麼請記住每一毫升的海水中

has about a million bacteria

都有大約100萬隻細菌

and on the order of 10 million viruses.

和大約1000萬隻病毒。

Less than 5,000 microbial species

到兩年前位置，只有少於五千種

have been characterized as of two years ago,

微生物被我們分類記載。

and so we decided to do something about it.

因此我們決定做些工作。

And we started the Sorcerer II Expedition,

我們啓動了‘魔法師二號’海巡計畫，

where we were, as with great oceanographic expeditions,

進行遠大的海洋考察，

trying to sample the ocean every 200 miles.

嘗試毎隔200英哩進行一次採樣。

We started in Bermuda for our test project,

我們先在百慕達進行前測。

then moved up to Halifax,

然後移師到哈利法克斯，

working down the U.S. East Coast,

一路往南經過美國東岸，

the Caribbean Sea, the Panama Canal,

加勒比海，巴拿馬運河，

through to the Galapagos, then across the Pacific,

穿過加拉巴哥群島，橫渡太平洋，

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

現在我們正在橫越

across the Indian Ocean.

印度洋的途中。

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

這是很吃重的工作；我們在帆船上進行此項任務，

in part to help excite young people

也是希望引起年輕人的興趣

about going into science.

來投身科學研究。

The experiments are incredibly simple.

實驗本身十分簡單。

We just take seawater and we filter it,

只要取得海水、經過過濾，

and we collect different size organisms on different filters,

通過不同的濾網來蒐集不同大小的微生物。

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

然後把它們的DNA帶回在岩城的實驗室，

where we can sequence a hundred million letters

在那裡我們可以在24小時內完成

of the genetic code every 24 hours.

一億個字符的基因編碼的測序。

And with doing this,

通過這樣做，

we've made some amazing discoveries.

我們有了驚人的新發現。

For example, it was thought that the visual pigments

舉例而言，一般認為人類眼中的視覺色素

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

在大自然中只有一兩種有機體

in the environment that had these same pigments.

擁有相同的色素。

It turns out, almost every species

結果發現幾乎所有生活在

in the upper parts of the ocean

氣候溫暖的地區的

in warm parts of the world

上層海域的物種

have these same photoreceptors,

都有這些感光細胞，

and use sunlight as the source of their energy

並且以陽光作為能量的來源

and communication.

並進行通訊。

From one site, from one barrel of seawater,

在一個地方取得的一桶海水中，

we discovered 1.3 million new genes

我們發現了130萬種新基因

and as many as 50,000 new species.

和多達5萬種新物種。

We've extended this to the air

目前我們獲得史隆基金的資助來

now with a grant from the Sloan Foundation.

把這種方法應用到對大氣圈中。

We're measuring how many viruses and bacteria

測量大家每天所呼吸的空氣中

all of us are breathing in and out every day,

病毒和細菌的數量，

particularly on airplanes

尤其是在飛機上

or closed auditoriums.

或是密閉的演講會場。

(Laughter)

(笑聲)

We filter through some simple apparatuses;

我們利用一些簡單的儀器過濾；

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

僅僅一天之內我們在紐約市的一棟大樓

filtering on top of a building in New York City.

的樓頂就蒐集到大約10億微生物。

And we're in the process of sequencing all that

目前我們正在對這些微生物

at the present time.

的基因進行測序。

Just on the data collection side,

在蒐集資料方面，

just where we are through the Galapagos,

當我們穿過加拉巴戈群島時，

we're finding that almost every 200 miles,

發現基本上每隔200英里，

we see tremendous diversity

我們所獲得的海水採樣中的

in the samples in the ocean.

生物種類就大不相同。

Some of these make logical sense,

這種多樣性有時候是很合理的，

in terms of different temperature gradients.

考慮到海水不同層面的水溫差異。

So this is a satellite photograph

這是一張反應溫度的

based on temperatures -- red being warm,

衛星照片－紅色是溫暖的地區，

blue being cold --

藍色則水溫較低－

and we found there's a tremendous difference between

我們發現來自高溫區和低溫區的海水樣本

the warm water samples and the cold water samples,

中的占主導數量的微生物種

in terms of abundant species.

顯示出極大差異。

The other thing that surprised us quite a bit

另一件讓人頗感驚訝的是

is these photoreceptors detect different wavelengths of light,

這些色素細胞會感應不同波長的光線，

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

可以利用胺基酸測序來估計這些情況。

And these vary tremendously from region to region.

這些特質在不同的區域也產生巨大的變化。

Maybe not surprisingly,

或許不完全那麼讓人吃驚的是，

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

在幾乎完全只有藍色的深海中，

the photoreceptors tend to see blue light.

感光細胞比較容易看見藍色的光線。

When there's a lot of chlorophyll around,

當周圍有大量葉綠素時，

they see a lot of green light.

它們感應到的就是綠光。

But they vary even more,

不過情況可能有更多的變化，

possibly moving towards infrared and ultraviolet

很可能會擴展到紅外線和紫外線

in the extremes.

這樣的極端的光線。

Just to try and get an assessment

為了評估

of what our gene repertoire was,

自然界基因庫的大小，

we assembled all the data --

我們匯整所有的資料

including all of ours thus far from the expedition,

包括所有目前實地採集的樣本，

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

它囊括地球一半以上的生物基因資料 －

and it totaled around 29 million genes.

總計大約有2千9百萬組基因。

And we tried to put these into gene families

我們嘗試把它們排進基因族譜

to see what these discoveries are:

以便獲得新的發現：

Are we just discovering new members of known families,

我們所發現的是已知族群中的新成員，

or are we discovering new families?

還是我們發現了新的族群？

And it turns out we have about 50,000

世界上大約有50，000

major gene families,

個主要的基因族群，

but every new sample we take in the environment

但是每一個我們從自然中獲取的新樣本

adds in a linear fashion to these new families.

都成為這些新族群的一個分支。

So we're at the earliest stages of discovery

因此對基礎的基因，

about basic genes,

及其成份和對生命的研究工作

components and life on this planet.

才是剛剛起步而已。

When we look at the so-called evolutionary tree,

在所謂的演化樹圖上，

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

人類位於右上角，跟動物在同一區。

Of those roughly 29 million genes,

在總共的大約2900萬種基因中，

we only have around 24,000

人類的基因組只具備其中

in our genome.

的大約2萬4千種。

And if you take all animals together,

如果把所有動物的基因算在一起，

we probably share less than 30,000

我們所共有的

and probably maybe a dozen

基因族群大概只有

or more thousand different gene families.

三萬不到一點。

I view that these genes are now

現在我並不認為這些基因

not only the design components of evolution.

僅僅只是是進化的的設計元素。

And we think in a gene-centric view --

我們從基因中心論來看－

maybe going back to Richard Dawkins' ideas --

或許回到了理查‧達金斯的想法

than in a genome-centric view,

而不是基因組中心論，

which are different constructs of these gene components.

那是以基因為組件所構造成的不同結果。

Synthetic DNA, the ability to synthesize DNA,

製造DNA以及製造它們的能力

has changed at sort of the same pace

與DNA測序技術以差不多的速度

that DNA sequencing has

從一二十年前發展至今，

over the last decade or two,

已經變得非常的省時

and is getting very rapid and very cheap.

並且成本低廉。

Our first thought about synthetic genomics came

我們關於人工制造基因組的想法起源

when we sequenced the second genome back in 1995,

與生殖道支原體，那是在95年我們做

and that from mycoplasma genitalium.

第二組基因組測序的時候。

And we have really nice T-shirts that say,

我們還做了漂亮的T恤衫

you know, "I heart my genitalium."

上面有寫「我愛我的生殖道」

This is actually just a microorganism.

生殖道支原體只是一種微生物。

But it has roughly 500 genes.

但有大約500對基因。

Haemophilus had 1,800 genes.

嗜血桿菌有1800對基因。

And we simply asked the question,

所以我們在想

if one species needs 800, another 500,

有的物種有800對基因，有的500，

is there a smaller set of genes

是否有更小的的基因組

that might comprise a minimal operating system?

是構成基本生物運作系統的基礎？

So we started doing transposon mutagenesis.

因此我們開始進行轉位子誘變。

Transposons are just small pieces of DNA

轉位子是隨即插入基因編碼

that randomly insert in the genetic code.

的小段的DNA。

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

如果置入基因的正中間，會阻斷其功能。

So we made a map of all the genes

我們將所有可以接受轉位子插入

that could take transposon insertions

的基因列在一張圖表上。

and we called those "non-essential genes."

我們稱之為「非必要基因」

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

不過我們發現環境起到了非常重要的作用，

and you can only

我們只能依據環境中

define an essential or non-essential gene

所存在的基因來定義一個基因是必要還是非必要。

based on exactly what's in the environment.

是必要還是非必要。

We also tried to take a more directly intellectual approach

我們還嘗試了更直接而巧妙的方法

with the genomes of 13 related organisms,

來研究13種相似有機物的基因組，

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

互相比較，尋找共性。

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

在其重疊的特性中，我們找到了173種基因。

common to all 13 organisms.

是這13種有機體所共有的。

The pool expanded a little bit if we ignored

如果不算其中一種細胞寄生物

one intracellular parasite;

共有的基因數量會略增。

it expanded even more

如果只考慮核心基因組

when we looked at core sets of genes

還會再多一些。

of around 310 or so.

大約310組。

So we think that we can expand

因此我們認為可以根據目標

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

來將前面所提到的最少的500組的基因組

to maybe 300 to 400 genes

擴展或者是縮減

from the minimal of 500.

至300到400組。

The only way to prove these ideas

唯一可以驗證這些想法的方法

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

就是製造一條包含有一些基因的染色體，

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

我們不得不以一種模塊式的方法來試驗。

We found that synthesizing accurate DNA

結果發現要精確地製造

in large pieces was extremely difficult.

大段的DNA超難的。

Ham Smith and Clyde Hutchison, my colleagues on this,

史密斯和賀金森，它們是我的兩位同事，

developed an exciting new method

研發出令人振奮的新方法

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

能讓我們在兩週內製造一隻

in only a two-week period

5000個鹼基對的病毒

that was 100 percent accurate,

基因序列和生物特性上

in terms of its sequence and its biology.

的精準度達到100%。

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

實驗非常令人振奮！就在我們將人造的DNA

injected it in the bacteria and all of a sudden,

植入細菌中的那一刻，

that DNA started driving the production of the virus particles

DNA立刻開始運作，製造病毒粒子

that turned around and then killed the bacteria.

反噬宿主，消滅了那隻細菌。

This was not the first synthetic virus --

這不是人造病毒的首度問世－

a polio virus had been made a year before --

小兒麻痺病毒一年前成功被製出

but it was only one ten-thousandth as active

但只有原病毒1/100的活性

and it took three years to do.

并且花了3年时间来制造。

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

這是噬菌體Phi X-174的結構图。

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

這是一個軟體能打造自身硬體的實際例子，

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

也是我們在生物學研究中的一個目標。

People immediately jump to concerns about biological warfare,

談到這些人們很容易就會產生對生物武器的擔憂，

and I had recent testimony before a Senate committee,

我最近在參議院委員會舉行前發表了證詞，

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

也參加了一個美國政府設立的的專門委員會來

to review this area.

監管這個領域。

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

我認為以對現實的深刻理解來應對

versus what happens with people's imaginations.

人們的空想是非常重要的。

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

基本上,今天任何已經完成測序的病毒

that genome can be made.

它們的基因組都可以人為製造。

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

人們會對馬上對伊波拉病毒或天花感到驚恐萬分，

but the DNA from this organism is not infective.

但這種人工病毒的DNA不具傳染性。

So even if somebody made the smallpox genome,

所以即使製造出天花的基因組，

that DNA itself would not cause infections.

DNA本身也不會造成傳染。

The real concern that security departments have

真正讓國安部門擔憂的

is designer viruses.

是特製的病毒。

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

世界上只有美國和前蘇聯兩國，

that had major efforts

曾經投注大量資源

on trying to create biological warfare agents.

企圖製造生物武器元件。

If that research is truly discontinued,

如果那些研究真的被終止了，

there should be very little activity

那將來在製造設計病毒上

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

就應該不會再有甚麼進展了。

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

我認為2年內就有可能製造出單細胞生物。

And possibly eukaryotic cells,

且很有可能在10年內

those that we have,

製造出人類身上

are possible within a decade.

也俱有的真核細胞。

So we're now making several dozen different constructs,

目前我們正在製作數十種不同的構造。

because we can vary the cassettes and the genes

因為我們可以變更這些放入

that go into this artificial chromosome.

人造染色体中的序列模块和基因。

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

关键问题是，如何与其他的部分排列在一起？

We start with these fragments,

我们 从 这些片段着手

and then we have a homologous recombination system

研发出了一个同源基因重组系统

that reassembles those into a chromosome.

能将这些片段组合进染色体当中

This is derived from an organism, deinococcus radiodurans,

这是从一种生物上得到的启发，

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

它能够承受三百万拉德（輻射計量單位）的辐射並且存活下來。

It reassembles its genome after this radiation burst

在輻射爆發過後它會在12至24小時內

in about 12 to 24 hours,

重組自己的基因，

after its chromosomes are literally blown apart.

在它的染色體被完全拆散後。

This organism is ubiquitous on the planet,

這種生物在地球上普遍存在，

and exists perhaps now

甚至可能因為我們飛上太空

in outer space due to all our travel there.

而也將它們帶進了宇宙。

This is a glass beaker after

這是經過50萬拉德輻射

about half a million rads of radiation.

照射過後的高腳酒杯。

The glass started to burn and crack,

玻璃開始 碎裂，

while the microbes sitting in the bottom

這微生物附在杯底

just got happier and happier.

越發的高興。

Here's an actual picture of what happens:

這是一張實際狀況的照片

the top of this shows the genome

上邊的圖片顯示的是經過一百七十萬

after 1.7 million rads of radiation.

拉德輻射後的基因組。

The chromosome is literally blown apart.

其染色體被完全粉碎。

And here's that same DNA automatically reassembled

而這邊十同樣的DNA經過

24 hours later.

24時後自行重組。

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

這些生物的能耐真是令人吃驚！

and we probably have thousands,

地球上大概存在着成千上萬種

if not tens of thousands, of different species

不同的物種擁有

on this planet that are capable of doing that.

這樣的能力。

After these genomes are synthesized,

在這些基因組被製造以後。

the first step is just transplanting them

第一步就是要將它們移植進

into a cell without a genome.

一個沒有基因組的細胞。

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

所以我們認為人造細胞將會有巨大的前景。

not only for understanding the basis of biology

不光是增進對生物學科最基本的理解

but for hopefully environmental and society issues.

希望也包括環境以及社會問題。

For example, from the third organism we sequenced,

例如，從我們所測序的第三個生物上

Methanococcus jannaschii -- it lives in boiling water temperatures;

詹氏甲烷鏈球菌：它生存在沸湯的水中

its energy source is hydrogen

其能量來源於氫

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

它所獲得的碳元素則從周圍環境中汲取。

So we know lots of different pathways,

我們瞭解到了許多不同的可能性，

thousands of different organisms now

數千種不同的生物

that live off of CO2,

以二氧化碳為生。

and can capture that back.

並能將其捕捉回來

So instead of using carbon from oil

與其從使用從石油中取得的

for synthetic processes,

來進行製造。

we have the chance of using carbon

我們可以選擇使用碳元素

and capturing it back from the atmosphere,

並將它從大氣層中捕捉回來，

converting that into biopolymers

轉化成生物高分子

or other products.

或者其他產品。

We have one organism that lives off of carbon monoxide,

還有一種微生物是依靠一氧化碳而存活的，

and we use as a reducing power

我們使用它作為一種低能耗的方式

to split water to produce hydrogen and oxygen.

來分解水來產生氫和氧。

Also, there's numerous pathways

同樣的也是有很多的

that can be engineered metabolizing methane.

被改造成排放出甲烷。

And DuPont has a major program with Statoil in Norway

杜邦正在於挪威石油公司開展一項重大的項目

to capture and convert the methane

從天然氣田中將甲烷捕獲

from the gas fields there into useful products.

並轉變成有用的商品。

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

不需要多久，我認為就會有一個全新的領域出現

called "Combinatorial Genomics,"

我們成為染色體重組

because with these new synthesis capabilities,

因為這些新的製造能力

these vast gene array repertoires

大量的基因群

and the homologous recombination,

以及同源重組方法的存在，

we think we can design a robot to make

我想我們可以設計一個機器人，

maybe a million different chromosomes a day.

每天可以製造或許百萬種不同的染色體。

And therefore, as with all biology,

所以，在生物學的試驗中，

you get selection through screening,

你可以通過篩選來達到目的。

whether you're screening for hydrogen production,

無論是想要獲得產生氫氣的特性，

or chemical production, or just viability.

或者化工生產，又或者是驗證某種生存性。

To understand the role of these genes

理解這些基因所發揮的功能

is going to be well within reach.

將會變得非常容易。

We're trying to modify photosynthesis

我們正在嘗試修改光合作用的過程

to produce hydrogen directly from sunlight.

當被當陽光照射後直接產生氫氣。

Photosynthesis is modulated by oxygen,

光合作用是由氧氣來調節的，

and we have an oxygen-insensitive hydrogenase

我們認為有一種氧不敏感的

that we think will totally change this process.

氢化酶將會完全改變這個過程。

We're also combining cellulases,

我們也在進行纤维素酶的混合，

the enzymes that break down complex sugars into simple sugars

將複雜糖分子拆解成簡單糖分子的酶

and fermentation in the same cell

在同一個培養皿里一起發酵

for producing ethanol.

來製造乙醇。

Pharmaceutical production is already under way

利用微生物進行製藥生產

in major laboratories

的實踐早已在各大

using microbes.

實驗室里展開。

The chemistry from compounds in the environment

這些從自然環境的組成部份中

is orders of magnitude more complex

獲的藥品比任何世界上最好的藥房

than our best chemists can produce.

所生產的還要複雜許多。

I think future engineered species

我認為將來通過改造的物種

could be the source of food,

可以成為食物的來源，

hopefully a source of energy,

希望也可以是能源的來源，

environmental remediation

環境的補救措施

and perhaps

或許

replacing the petrochemical industry.

替代整個化工行業。

Let me just close with ethical and policy studies.

請讓我以倫理以及政策的研究來做結尾。

We delayed the start of our experiments in 1999

在1999年我們延遲了試驗的開始

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

直到我們完成了一個一年半的生物倫理審核

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

是否應該嘗試製造人造物種。

Every major religion participated in this.

每一個主要的宗教都參與了這個審核。

It was actually a very strange study,

其實這是一個非常奇怪的研究，

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

因為各種宗教領袖使用他們的教義作為律法，

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

卻找不到任何關於禁止創造生命的條款，

so it must be OK. The only ultimate concerns

所以這方面就沒問題了。最終的

were biological warfare aspects of this,

卻是生物戰的方面的擔憂，

but gave us the go ahead to start these experiments

為我們亮起繼續

for the reasons we were doing them.

這些試驗的綠燈。

Right now the Sloan Foundation has just funded

史隆基金會為此剛剛資助了

a multi-institutional study on this,

一個多機構的研究項目，

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

來分析出該項技術對社會而言所存在的風險與益處，

and the rules that scientific teams such as my own

以及各個科研團隊就比如我自己的團隊

should be using in this area,

所應該在這個領域遵守的準則。

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

隨著前進過程中我們試着樹立起一個好的榜樣。

These are complex issues.

有許多復長複雜的問題。

Except for the threat of bio-terrorism,

不包括生物恐怖襲擊的威脅，

they're very simple issues in terms of,

那些其實是簡單的多的狀況。

can we design things to produce clean energy,

是否能夠設計用來產生結晶能源的物種，

perhaps revolutionizing

甚至對發展中國家

what developing countries can do

的生產方式進行革新

and provide through various simple processes.

提供各種便捷的處理方法。

Thank you very much.

謝謝！