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

翻译人员: JENNY SUN 校对人员: Grace Man

So we built a virus-resistant organism.

所以我们建立了 一个抗病毒的有机体系。

Why?

为什么？

It's not about disease, or not directly.

这与疾病无关，或者说 不直接与疾病有关。

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

它是关于建立未来的清洁工厂。

Let me explain by taking a big step back.

让我退一步来解释。

All life runs on DNA.

所有的生命都依赖 DNA 运行。

DNA codes for proteins, and proteins run life.

DNA 为蛋白质编码， 而蛋白质则掌管着生命。

DNA is composed of four bases:

DNA 由四个主要成分组成：

A, T, G and C.

A、T、G和C。

And triplets of these bases, known as codons,

这些三个一组（三联体）的 主要成分，称为密码子，

encode each of the amino acid building blocks in proteins.

编码蛋白质中的 每个氨基酸组成部分。

The genetic code is a rulebook

遗传密码是一本规则手册，

that defines which codon encodes which amino acid.

它定义了哪个密码子 编码哪个氨基酸。

So, for example,

因此，例如，

the triplet codon TCG encodes the amino acid serine.

三联体的密码子 TCG 编码氨基酸丝氨酸。

And the order of triplet codons in DNA

DNA 中三联体的密码子的顺序

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

编码了蛋白质中氨基酸 构建模块的顺序。

There are 64 triplet codons in DNA

DNA 中有 64 个 三联体的密码子，

and just 20 common amino acids.

只有 20 个常见氨基酸。

And this means that most amino acids

这意味着大多数氨基酸

are encoded by more than one triplet codon.

是由超过一个 三联体的密码子编码的。

So, for example, the amino acid serine

因此，例如，氨基酸丝氨酸

is encoded by six different triplet codons.

是由六个不同的 三联体的密码子编码的。

And triplet codons that encode the same amino acid

编码相同氨基酸的三联体的密码子

are defined as synonymous codons.

被定义为同义密码子。

The DNA code used for life is near universal.

生命所用的 DNA 密码几乎是通用的。

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

所有的生命形式和病毒都使用 基本相同的遗传密码。

And that's a trait that we can exploit.

而这也是我们可以利用的一个特点。

Here's what we did.

这就是我们所做的。

We asked whether life needs multiple synonymous codons

我们想知道生命 是否需要多个同义密码子

to encode a single amino acid.

来编码单个氨基酸。

For example, does life need six different codons,

例如，生命是否需要 六个不同的密码子，

which all code for the amino acid serine?

而这些密码子 都是编码氨基酸丝氨酸的？

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

我们拿了四百万个字符的 大肠杆菌的 DNA 及其基因组，

and completely rewrote the code of this microbe

以非常特定的方式完全改写了

in a very specific way

这种微生物的密码，

by replacing targeted codons in its genome

我们通过用编码 相同氨基酸的同义密码子

with synonymous codons that encode the same amino acid.

替换其基因组中的目标密码子。

So for example,

因此，举例来说，

we replaced the TCG and TCA codons,

我们将编码氨基酸丝氨酸的

which encode the amino acid serine,

TCG 和 TCA 密码子

with AGT and AGC codons,

替换为 AGT 和 AGC 密码子，

which also encode the amino acid serine.

后者也编码氨基酸丝氨酸。

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

通过在整个 400 万个碱基的 基因组中这样做，

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

我们从大肠杆菌的遗传密码中 完全去除了目标密码子。

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

总的来说，我们将遗传密码 从使用 64 个密码子

压缩到使用 61 个密码子。

How did we do it?

我们是怎么做到的？

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

我们首先将 400 万个特征的 代码放在计算机中，

and used a find-and-replace operation

使用查找和替换操作

to replace targeted codons with their synonyms.

将目标密码子替换为其同义词。

This created our new genome design,

这创造了我们新的基因组设计，

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

其中包含相对于原始基因组的 18,000 多个变化。

We then asked whether we could build an organism

然后我们想知道 我们是否可以构建一个

that runs on our synthetic genome design.

在我们的合成基因组设计上 运行的有机体。

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

我们从短的 DNA 片段开始 构建合成基因组。

These were made by chemistry in a test tube,

这些是在试管中 通过化学方法制成的，

something that would have been prohibitively expensive to do

这在十年或二十年前， 这种规模的制造成本

on this scale just a decade or two ago.

高得令人望而却步。

We then assembled these short pieces of DNA

然后我们将这些 短 DNA 片段组装成

into longer stretches of DNA,

更长的 DNA 片段，

which we then used to step-by-step replace

然后我们用这些片段逐步替换

all four million bases of the E. coli genome.

大肠杆菌基因组的 所有 400 万个碱基。

This created the largest synthetic genome ever made.

这创造了有史以来 最大的合成基因组。

And the resulting cell was alive.

由此产生的细胞是活的。

Think about that.

想一想。

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

我们简化了遗传密码， 但细胞仍然活着。

We can create life with a compressed genetic code.

我们可以用压缩的遗传密码 创造生命。

Now because our organism with a compressed genetic code

现在，由于我们具有 浓缩遗传密码的生物体，

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

不使用所有 64 个三联体的 密码子来制造蛋白质，

we could remove some of the machinery from the cell

我们可以从细胞中移除一些

that normally reads the near-universal genetic code.

通常读取近乎普遍的 遗传密码的机制。

Specifically, we could remove components of the translational machinery,

具体来说，我们可以移除 转化体系的成分，

specific tRNAs,

即特定的 tRNAs，

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

它们通常会读取我们从基因组中 移除的密码子。

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

现在，这里的关键点是我们 已经创建了一个细胞，

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

它不再读取几乎普遍的 遗传密码中的所有密码子。

Now viruses infect cells.

现在病毒感染细胞。

These might be the cells of our bodies

这些可能是我们身体的细胞

or single-celled microbes like E.coli.

或像大肠杆菌这样的 单细胞微生物。

They commonly have their own DNA,

它们通常有自己的 DNA，

which uses the near-universal genetic code

它使用近乎通用的遗传密码

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

来编码复制病毒所需的蛋白质。

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

但是病毒没有读取其 DNA 中 遗传密码的机制，

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

而是依靠宿主细胞， 即宿主细胞的机制

to read the genetic code in their DNA

来读取其 DNA 中的遗传密码

and make copies of the virus.

并复制病毒。

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

正是这些病毒副本 继续感染其他细胞。

And this is how viruses spread.

这就是病毒传播的方式。

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

但病毒无法在我们的 新生物体中复制自己，

because our new organism doesn't have the machinery

因为我们的新生物体没有

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

读取病毒 DNA 中 所有密码子的机制。

The code in the DNA used in the virus

病毒中使用的 DNA 中的代码

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

与宿主细胞读取 该代码的机制是不兼容的。

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

因此，病毒不会在新生物体内传播，

and the new organism is resistant to viruses.

而且新生物体对病毒具有抵抗力。

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

事实上，我们证明了我们的新生物体 对多种病毒具有抗性，

suggesting that rewriting the genetic code

这表明重写遗传密码

provides a route to creating broadly virus-resistant life.

提供了一条创造 广泛抗病毒生命的途径。

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

通过将我们开发的方法 扩展到其他生物体，

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

有可能会创造出 抗病毒的作物和动物，

with important applications in agriculture and beyond.

在农业和其他领域有重要的应用。

But our advances also provide a foundation

但我们的进步

for turning cells into the clean factories of the future.

也为将细胞转变为未来的 清洁工厂奠定了基础。

How?

如何做呢？

So to explain, let me take another step back

所以，为了解释，让我再回到

to how organisms read their genetic code to make proteins.

有机体如何读取其遗传密码 来制造蛋白质。

Recall that the order of triplet codons in DNA

回想一下，DNA 中 三联体的密码子的顺序

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

编码了蛋白质中 氨基酸结构单元的顺序。

And it's the translational machinery of cells

是细胞的转换机制

that reads the triplet codons

读取三联体的密码子

and builds the corresponding sequence of amino acids.

并构建相应的氨基酸序列。

The translational machinery of natural cells --

天然细胞的转换机制——

including ribosomes,

包括核糖体、

aminoacyl-tRNA synthetase enzymes and tRNAs --

氨酰基-tRNA合成酶和tRNAs——

is a unique and special system for making proteins

是一种用于制造蛋白质的 独特而特殊的系统，

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

其中 20 种常见的氨基酸 串在一起形成一条链。

Now, proteins are amazing,

现在，蛋白质很神奇，

but they're just one example

但它们只是被称为

from a vast class of molecules known as polymers,

聚合物的一大类分子的一个例子，

which includes plastics, materials and drugs.

其中包括塑料、材料和药物。

And the polymer or linear polymer is really any molecule

聚合物或线性聚合物 实际上是任何分子

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

其中更简单的化学结构单元 串在一起形成链。

We wanted to unlock the potential of the translational machinery

我们希望释放出转化机制的潜力

for making plastics, materials and drugs

用于制造塑料、材料和药物，

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

这些塑料、材料和药物 根本无法以任何其他方式制造，

or that could be made more cleanly and efficiently

或者可以使用 细胞转化机制的改造方式

using engineered versions of the cell's translational machinery.

可以更清洁、更有效地实现这一点。

The building blocks for these polymers

这些聚合物的组成部分

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

远远超出了用于制造 蛋白质的 20 种常见氨基酸。

It's been impossible to unlock the potential

它不可能释放

of the translational machinery for making plastics, materials and drugs

用于制造塑料、材料和药物的 转化机制的潜力。

for two reasons.

由于两个原因。

First, all 64 triplet codons in natural cells

首先，天然细胞中的所有 64 个三联体密码子

are used for making natural proteins,

都用于制造天然蛋白质，

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

而且根本没有可用于编码 新聚合物合成的密码子。

Second, the natural translational machinery

其次，天然的转换机制

specifically uses natural amino acids

专门使用天然氨基酸，

and simply can't use the chemical building blocks

根本无法使用制造

required to make new polymers.

新聚合物所需的化学构件。

However, a virus-resistant organism

然而，抗病毒生物体

doesn't use all 64 triplet codons to make proteins

不会使用所有 64 个三联体的 密码子来制造蛋白质，

and doesn't contain the machinery to read the codons

并且不包含读取

that have been deleted from its genome.

已从其基因组中 删除的密码子的机制。

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

这个细胞为基因编码的聚合物合成 提供了起点。

To realize genetically-encoded polymer synthesis

为了在我们的抗病毒生物体中

in our virus-resistant organism,

实现基因编码的聚合物合成，

we added synthetic DNA containing the triplet codons

我们添加了含有

we'd removed from the genome of the cell

我们从细胞的基因组中移除的 三联体密码子的合成 DNA，

and engineered translational machinery to read these codons

并设计了转化机制来 读取这些密码子，

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

并将它们重新分配到 新的化学构件中，用于新的聚合物。

This system can be programmed to make diverse synthetic polymers.

该系统可以编程 以制造各种合成聚合物。

By changing the order of the triplet codons

通过改变合成 DNA 中

in the synthetic DNA,

三联体密码子的顺序，

we can change the order of the chemical building blocks

我们可以改变我们在生成的聚合物中

that we program into the resulting polymer.

编程的化学构件的顺序。

And by changing the identity of the engineered translational machinery

通过改变我们添加到细胞中的

that we add to the cell,

设计转换机制的特性，

we can change the identity of the chemical building blocks

我们可以改变我们构成聚合物的

from which we compose the polymer.

化学构件的特性。

Overall, we've created a cellular factory

总体而言，我们已经创建了 一个细胞工厂，

that we can reliably and predictably program

我们可以通过可靠且可预测的编程

to make synthetic polymers.

来制造合成聚合物。

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

使用我们的方法， 我们已经能够对细胞进行编程

to make new molecules,

以制造新分子，

including molecules from an important class of drugs

包括来自被称为缩肽大环化合物

known as depsipeptide macrocycles.

一类重要药物的分子。

Molecules in this class include antibiotics,

此类分子包括抗生素、

immunosuppressives and anti-tumor compounds.

免疫抑制剂和抗肿瘤化合物。

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

我们还能够对细胞进行编程， 以制造完全合成的聚合物，

containing the chemical linkages found

其中包含在几类

in several classes of biodegradable plastics.

可生物降解塑料中发现的化学连接。

As we build new polymer molecules using our cellular factories,

当我们使用我们的细胞工厂 制造新的聚合物分子时，

we have the opportunity to consider from the beginning

我们有机会从一开始就考虑

how we might also use engineered biological cells

如何使用改造的生物细胞

to break these polymers down

来分解这些聚合物，

into their constituent chemical building blocks

将其分解为

that could be recycled and used for new encoded polymers.

可以回收的化学成分 并用于新的编码聚合物。

We envision a circular bioeconomy

我们设想了一种循环生物经济，

in which our new genetically-encoded plastics and materials

在这种经济中，其中我们的 新基因编码塑料和材料

are manufactured and ultimately broken down

是利用现有的生物反应器 和发酵罐制造出来

using low-energy cellular processes,

并使用低能量细胞过程

taking advantage of existing bioreactors and fermenters.

最终将其分解。

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

通过从大自然中汲取灵感并重新想象 生命可以变成什么样子，

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

我们有机会建立未来的可持续产业。

Thank you.

谢谢。

(Applause)

（掌声）