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

    譯者: Tom Lin 審譯者: Yi-Jyun Luo

  • 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

  • it's going to be a huge challenge.

    或者任何能替代它的方法,

  • Then of course, there's all that

    這會是一個巨大的挑戰。

  • CO2 from this material

    接下來,當然,

  • that ends up in the atmosphere.

    這份資料是關於CO2

  • We now, from our discovery around the world,

    被排放在大氣層中的二氧化碳。