A Virus-Resistant Organism -- and What It Could Mean for the Future | Jason W. Chin | TED

譯者: Ivy Hung 審譯者: Shelley Tsang 曾雯海

So we built a virus-resistant organism.

我們建造了一個抗病毒的生物體。

Why?

為什麼？

It's not about disease, or not directly.

這與疾病無關，不是直接的。

It's about building the clean factories of the future.

這有關建立未來乾淨的工廠。

Let me explain by taking a big step back.

讓我退後一大步來解釋。

All life runs on DNA.

所有生命都依靠 DNA 運行。

DNA codes for proteins, and proteins run life.

DNA為蛋白質編碼，而蛋白質運行生命。

DNA is composed of four bases:

DNA由四個鹼基組成：

A, T, G and C.

A、T、G 和 C。

And triplets of these bases, known as codons,

這些鹼基的三胞胎，稱為密碼子，

encode each of the amino acid building blocks in proteins.

編碼著每個組成蛋白質的氨基酸。

The genetic code is a rulebook

遺傳密碼是一本規則手冊

that defines which codon encodes which amino acid.

規定哪個密碼子編碼哪個氨基酸。

So, for example,

所以，例如，

the triplet codon TCG encodes the amino acid serine.

三聯密碼子TCG 編碼著稱絲氨酸的氨基酸。

And the order of triplet codons in DNA

而DNA中三聯體密碼子的順序

encodes the order of amino acid building blocks in a protein.

決定組成蛋白質的氨基酸的順序。

There are 64 triplet codons in DNA

DNA中有64個三聯體密碼子

and just 20 common amino acids.

以及 20 種常見氨基酸。

And this means that most amino acids

這意味著大多數氨基酸

are encoded by more than one triplet codon.

被多於一種的三聯體密碼子編碼。

So, for example, the amino acid serine

例如，氨基酸絲氨酸

is encoded by six different triplet codons.

由六種不同的三聯體密碼子編碼。

And triplet codons that encode the same amino acid

而編碼相同的氨基酸的三聯體密碼子

are defined as synonymous codons.

被定義為同義密碼子。

The DNA code used for life is near universal.

用於生命的DNA密碼 幾乎通行於全物種。

All forms of life and viruses use essentially the same genetic code.

所有形式的生命和病毒 使用本質上相同的遺傳密碼。

And that's a trait that we can exploit.

這是我們可以利用的特徵。

Here's what we did.

這就是我們所做的。

We asked whether life needs multiple synonymous codons

我們問生命是否需要 多個同義密碼子

to encode a single amino acid.

編碼同一個氨基酸。

For example, does life need six different codons,

例如，生命是否需要 六種不同的密碼子

which all code for the amino acid serine?

來編碼同一個叫絲氨酸的氨基酸?

We took the four-million-character DNA of E. coli, its genome,

我們拿了四百萬字 大腸桿菌的 DNA，它的基因組，

and completely rewrote the code of this microbe

並以一種非常特定的方式 完全改寫這種微生物的編碼

in a very specific way

by replacing targeted codons in its genome

用同樣編碼該胺基酸的同義密碼子 替代基因組中的目標密碼子。

with synonymous codons that encode the same amino acid.

So for example,

例如，

we replaced the TCG and TCA codons,

我們替除 TCG 和 TCA 密碼子，

which encode the amino acid serine,

它們編碼氨基酸絲氨酸，

with AGT and AGC codons,

而用 AGT 和 AGC 密碼子替代，

which also encode the amino acid serine.

因它們也是編碼氨基酸絲氨酸。

By doing this across the whole four-million-base genome,

透過對整個四百萬個鹼基的基因組這樣做，

we completely removed the targeted codons from the genetic code of E. coli.

我們完全替除來自大腸桿菌基因編碼的目標密碼子。

Overall, we compressed the genetic code from using 64 codons to using 61 codons.

總之，我們將基因編碼 從64個密碼子壓縮到只用61個密碼子。

How did we do it?

我們是怎麼做的？

We first took the four-million-character code in a computer

我們先把四百萬字的代碼放進電腦

and used a find-and-replace operation

並使用了查找和替換的操作

to replace targeted codons with their synonyms.

來用同義詞替換目標密碼子。

This created our new genome design,

這創造了我們新的基因組設計，

which contained more than 18,000 changes with respect to the original genome.

其中相對於原始基因組 包含超過 18,000 個更改。

We then asked whether we could build an organism

然後我們問我們是否可以創造一個生物

that runs on our synthetic genome design.

用我們的合成基因組設計上運行。

We built the synthetic genome starting from short pieces of DNA.

我們從短的 DNA 片段開始構建了合成基因組。

These were made by chemistry in a test tube,

這些是在試管中由化學製成的，

something that would have been prohibitively expensive to do

這樣的規模在十幾二十幾年前非常非常昂貴。

on this scale just a decade or two ago.

We then assembled these short pieces of DNA

然後我們組裝這些短的 DNA 片段

into longer stretches of DNA,

成更長的DNA鏈，

which we then used to step-by-step replace

然後我們用它來逐步替換

all four million bases of the E. coli genome.

所有大腸桿菌基因組四百萬個鹼基。

This created the largest synthetic genome ever made.

這創造了最大的 曾經做過的合成基因組。

And the resulting cell was alive.

產生的細胞是活的。

Think about that.

想一下。

We streamlined the genetic code, and yet the cell lived.

我們簡化了遺傳密碼， 然而細胞還活著。

We can create life with a compressed genetic code.

我們可以用壓縮的遺傳密碼創造生命。

Now because our organism with a compressed genetic code

現在因為我們帶有壓縮遺傳密碼的生物

doesn't use all 64 triplet codons to make proteins,

不使用全部 64 個三聯體密碼子 製造蛋白質，

we could remove some of the machinery from the cell

我們可以去除一些原本在細胞中 辨識幾乎所有基因編碼的機制。

that normally reads the near-universal genetic code.

Specifically, we could remove components of the translational machinery,

具體來說，我們可以刪除轉譯機制的某些組件，

specific tRNAs,

特定的 tRNA,

that normally read the codons that we've removed from the genome.

它們曾經讀取 我們已經從基因組中刪除的密碼子。

Now, the key point here is that we've created a cell

現在，關鍵點是我們在這裡創建了一個

that no longer reads all the codons in the near-universal genetic code.

不再讀取 通用近乎所有生物的遺傳密碼密碼子的細胞

Now viruses infect cells.

病毒感染細胞。

These might be the cells of our bodies

這些可能是我們身體的細胞

or single-celled microbes like E.coli.

或大腸桿菌等單細胞微生物的細胞。

They commonly have their own DNA,

他們通常有自己的DNA，

which uses the near-universal genetic code

使用近乎通用所有生物的遺傳密碼

to encode the proteins necessary to make copies of the virus.

來編碼可以製作病毒副本的蛋白質。

But viruses don't have the machinery to read the genetic code in their DNA,

但是病毒沒有讀取他們DNA中的遺傳密碼的機制，

and instead they rely on the host cell, the machinery of the host cell,

相反，它們依賴於宿主細胞， 宿主細胞的機制，

to read the genetic code in their DNA

來讀取他們 DNA 中的遺傳密碼

and make copies of the virus.

並複制病毒。

It's these copies of the virus that go on to infect other cells.

就是這些病毒的副本 繼續感染其他細胞。

And this is how viruses spread.

這就是病毒傳播的方式。

But viruses are unable to make copies of themselves in our new organism

但是病毒無法在我們的新生物體中複製

because our new organism doesn't have the machinery

因為我們的新生物 沒有閱讀病毒DNA中所有密碼子的機制。

to read all the codons in the DNA of the virus.

The code in the DNA used in the virus

病毒中使用的 DNA 中的代碼

and the host cell's machinery to read that code are incompatible.

和宿主細胞用來閱讀編碼的機制是不合的。

Therefore, the virus doesn’t spread in the new organism,

因此，病毒不會傳播 在新的生物中，

and the new organism is resistant to viruses.

而新生物對病毒有抵抗力。

In fact, we showed that our new organism was resistant to a wide range of viruses,

事實上，我們證明了我們的新生物 對多種病毒具有抵抗力，

suggesting that rewriting the genetic code

這表示重寫遺傳密碼

provides a route to creating broadly virus-resistant life.

提供創建抵抗大部分病毒的生命的路徑。

By extending the approaches we've developed to other organisms,

將我們發展的方法延伸到其他生物，

it may be possible to create virus-resistant crops and animals

有可能創造抗病毒作物和動物

with important applications in agriculture and beyond.

在農業及其他領域具有重要應用。

But our advances also provide a foundation

我們的進展也提供轉變細胞成未來乾淨工廠的基礎。

for turning cells into the clean factories of the future.

How?

怎麼做?

So to explain, let me take another step back

所以要解釋，讓我再退一步解釋

to how organisms read their genetic code to make proteins.

生物體如何閱讀他們的遺傳密碼 來製造蛋白質。

Recall that the order of triplet codons in DNA

回想一下 DNA 中的三聯密碼子的順序

encodes the order of amino acid building blocks in a protein.

編碼組成蛋白質的氨基酸的順序。

And it's the translational machinery of cells

正是細胞中的轉譯機制

that reads the triplet codons

閱讀密碼子三聯體

and builds the corresponding sequence of amino acids.

並建造對應的氨基酸序列。

The translational machinery of natural cells --

天然細胞的翻譯機制--

including ribosomes,

包含核醣體，

aminoacyl-tRNA synthetase enzymes and tRNAs --

氨酰tRNA合成酶，酶，和 tRNAs --

is a unique and special system for making proteins

是一個用於製造蛋白質 獨特而特殊的系統

in which the 20 common amino acids are strung together in a chain.

其中將20種常見氨基酸 串成一條鏈。

Now, proteins are amazing,

蛋白質超棒的，

but they're just one example

但他們只是來自被稱為聚合物的 諸多大分子的一個例子，

from a vast class of molecules known as polymers,

which includes plastics, materials and drugs.

其中包括塑料，材料，和藥物。

And the polymer or linear polymer is really any molecule

聚合物或線性聚合物 真的是任何被簡單化學物質串成一鏈的分子

in which simpler chemical building blocks are strung together in a chain.

We wanted to unlock the potential of the translational machinery

我們想釋放翻譯機制的潛力

for making plastics, materials and drugs

於製造塑料、材料、和藥物

that simply can't be made in any other way,

那根本以任何其他方式做不到，

or that could be made more cleanly and efficiently

或者可以運用編輯過的細胞翻譯機制 做得更乾淨、更高效。

using engineered versions of the cell's translational machinery.

The building blocks for these polymers

這些聚合物的組成部分 遠遠超過用於製造蛋白質的 20 種常見氨基酸。

go well beyond the 20 common amino acids used to make proteins.

It's been impossible to unlock the potential

打開製作塑料、材料、和藥物翻譯機制的淺能 因為兩個原因幾乎不不可能。

of the translational machinery for making plastics, materials and drugs

for two reasons.

First, all 64 triplet codons in natural cells

首先，所有在自然細胞中 64 個三聯體密碼子

are used for making natural proteins,

被用於製造天然蛋白質，

and there are simply no codons available to encode the synthesis of new polymers.

並且根本沒有可用的密碼子 編碼新聚合物的合成。

Second, the natural translational machinery

第二、自然的翻譯機制

specifically uses natural amino acids

專門使用天然氨基酸

and simply can't use the chemical building blocks

根本無法使用製造新聚合物 必要的化學積木。

required to make new polymers.

However, a virus-resistant organism

然而，抗病毒的生物體

doesn't use all 64 triplet codons to make proteins

不使用全部 64 個三聯體密碼子 來製造蛋白質

and doesn't contain the machinery to read the codons

並且缺乏 閱讀已從其基因組中刪除密碼子的機制。

that have been deleted from its genome.

And this cell provides the starting point for genetically-encoded polymer synthesis.

這個細胞提供用 於遺傳編碼聚合物合成的起點。

To realize genetically-encoded polymer synthesis

為了在在我們的抗病毒生物體中實現 遺傳編碼聚合物合成，

in our virus-resistant organism,

we added synthetic DNA containing the triplet codons

我們添加了我們從細胞的基因組中移除的 含有三聯密碼子的合成 DNA

we'd removed from the genome of the cell

and engineered translational machinery to read these codons

並編輯了閱讀這些密碼子的機制

and reassign them to new chemical building blocks for new polymers.

並重新分配給新聚合物的新化學積木。

This system can be programmed to make diverse synthetic polymers.

這個系統可以編程 製造多種合成聚合物。

By changing the order of the triplet codons

透過改變合成的DNA中三聯密碼子的順序，

in the synthetic DNA,

we can change the order of the chemical building blocks

我們可以改變我們編進聚合物 的化學積木順序。

that we program into the resulting polymer.

And by changing the identity of the engineered translational machinery

而透過改變我們加進細胞， 編輯過的機制的身分，

that we add to the cell,

we can change the identity of the chemical building blocks

我們可以改變我們組成聚合物 化學積木的身分。

from which we compose the polymer.

Overall, we've created a cellular factory

總之，我們已經創建了一個細胞工廠

that we can reliably and predictably program

一個我們可以有效預測編輯 來製造合成聚合物。

to make synthetic polymers.

Using our approach, we've already been able to program cells

使用我們的方法， 我們已經能夠對細胞進行編程

to make new molecules,

來製造新分子，

including molecules from an important class of drugs

包括來自一類重要的藥物的分子，

known as depsipeptide macrocycles.

稱為depsipeptide macrocycles。

Molecules in this class include antibiotics,

此類分子包括抗生素，

immunosuppressives and anti-tumor compounds.

免疫抑製劑和抗腫瘤化合物。

We've also been able to program cells to make completely synthetic polymers

我們也已經能夠編輯細胞 來製造完全合成的聚合物

containing the chemical linkages found

包含在幾類生物降解塑料可找到的化學鍵結。

in several classes of biodegradable plastics.

As we build new polymer molecules using our cellular factories,

當我們使用我們的細胞工廠 構建新的聚合物分子時，

we have the opportunity to consider from the beginning

我們有機會自一開始就思考

how we might also use engineered biological cells

我們要怎麼利用編輯過的生物細胞

to break these polymers down

來分解這些聚合物

into their constituent chemical building blocks

成組成他們的化學積木

that could be recycled and used for new encoded polymers.

可以回收的 並用於新的編碼聚合物。

We envision a circular bioeconomy

我們設想循環生物經濟

in which our new genetically-encoded plastics and materials

其中我們新的基因編碼 製造的塑料和材料

are manufactured and ultimately broken down

使用低能量細胞過程製造並最終分解，

using low-energy cellular processes,

taking advantage of existing bioreactors and fermenters.

利用現有的 生物反應器和發酵槽。

By taking inspiration from nature and reimagining what life can become,

從大自然中汲取靈感 重新想像生活會變成什麼樣子，

we have the opportunity to build the sustainable industries of the future.

我們有機會建立 未來的永續產業。

Thank you.

謝謝。

(Applause)

（掌聲）