TED演講者：Jason W. Chin / 杰森·W·錢

演講標題：A virus-resistant organism -- and what it could mean for the future / 一種抗病毒生物體——以及它對未來可能的意義

內(nèi)容概要：What if we could use the power of DNA to create a sustainable, circular economy? In a talk about breakthrough science, synthetic biologist Jason W. Chin describes his team's work rewriting the genetic blueprint of cells to create a virus-resistant organism -- the largest synthetic genome ever made and a first step towards reimagining what life can become. Learn more about how this advancement could lay the groundwork for the sustainable factories of the future, capable of producing plastics, antibiotics and more.

如果我們可以利用 DNA 的力量創(chuàng)造可持續(xù)的循環(huán)經(jīng)濟會怎樣？ 在一次關于突破性科學的演講中，合成生物學家杰森·W·錢（Jason W. Chin） 描述了他的團隊正在改寫細胞的基因圖譜以創(chuàng)造一種抗病毒生物體——這是有史以來最大的合成基因組，也是重新構想生命可以成為什么的第一步。 詳細了解這一進步如何為未來的可持續(xù)工廠奠定基礎，這些工廠能夠生產(chǎn)塑料、抗生素等。

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【1】So we built a virus-resistant organism.

所以我們建立了 一個抗病毒的有機體系。

【2】Why?

為什么？

【3】It's not about disease, or not directly.

這與疾病無關,或者說 不直接與疾病有關。

【4】It's about building the clean factories of the future.

它是關于建立未來的清潔工廠。

【5】Let me explain by taking a big step back.

讓我退一步來解釋。

【6】All life runs on DNA.

所有的生命都依賴 DNA 運行。

【7】DNA codes for proteins, and proteins run life.

DNA 為蛋白質編碼, 而蛋白質則掌管著生命。

【8】DNA is composed of four bases: A, T, G and C.

DNA 由四個主要成分組成: A、T、G和C。

【9】And triplets of these bases, known as codons, encode each of the amino acid building blocks in proteins.

這些三個一組（三聯(lián)體）的 主要成分,稱為密碼子, 編碼蛋白質中的 每個氨基酸組成部分。

【10】The genetic code is a rulebook that defines which codon encodes which amino acid.

遺傳密碼是一本規(guī)則手冊, 它定義了哪個密碼子 編碼哪個氨基酸。

【11】So, for example, the triplet codon TCG encodes the amino acid serine.

因此,例如, 三聯(lián)體的密碼子 TCG 編碼氨基酸絲氨酸。

【12】And the order of triplet codons in DNA encodes the order of amino acid building blocks in a protein.

DNA 中三聯(lián)體的密碼子的順序 編碼了蛋白質中氨基酸 構建模塊的順序。

【13】There are 64 triplet codons in DNA and just 20 common amino acids.

DNA 中有 64 個 三聯(lián)體的密碼子, 只有 20 個常見氨基酸。

【14】And this means that most amino acids are encoded by more than one triplet codon.

這意味著大多數(shù)氨基酸 是由超過一個 三聯(lián)體的密碼子編碼的。

【15】So, for example, the amino acid serine is encoded by six different triplet codons.

因此,例如,氨基酸絲氨酸 是由六個不同的 三聯(lián)體的密碼子編碼的。

【16】And triplet codons that encode the same amino acid are defined as synonymous codons.

編碼相同氨基酸的三聯(lián)體的密碼子 被定義為同義密碼子。

【17】The DNA code used for life is near universal.

生命所用的 DNA 密碼幾乎是通用的。

【18】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 基本相同的遺傳密碼。

【19】And that's a trait that we can exploit.

而這也是我們可以利用的一個特點。

【20】Here's what we did.

這就是我們所做的。

【21】We asked whether life needs multiple synonymous codons to encode a single amino acid.

我們想知道生命 是否需要多個同義密碼子 來編碼單個氨基酸。

【22】For example, does life need six different codons, which all code for the amino acid serine?

例如,生命是否需要 六個不同的密碼子, 而這些密碼子 都是編碼氨基酸絲氨酸的？

【23】We took the four-million-character DNA of E. coli, its genome, and completely rewrote the code of this microbe in a very specific way by replacing targeted codons in its genome with synonymous codons that encode the same amino acid.

我們拿了四百萬個字符的 大腸桿菌的 DNA 及其基因組, 以非常特定的方式完全改寫了 這種微生物的密碼, 我們通過用編碼 相同氨基酸的同義密碼子 替換其基因組中的目標密碼子。

【24】So for example, we replaced the TCG and TCA codons, which encode the amino acid serine, with AGT and AGC codons, which also encode the amino acid serine.

因此,舉例來說, 我們將編碼氨基酸絲氨酸的 TCG 和 TCA 密碼子 替換為 AGT 和 AGC 密碼子, 后者也編碼氨基酸絲氨酸。

【25】By doing this across the whole four-million-base genome, we completely removed the targeted codons from the genetic code of E. coli.

通過在整個 400 萬個堿基的 基因組中這樣做, 我們從大腸桿菌的遺傳密碼中 完全去除了目標密碼子。

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

總的來說,我們將遺傳密碼 從使用 64 個密碼子

【27】How did we do it?

我們是怎么做到的？

【28】We first took the four-million-character code in a computer and used a find-and-replace operation to replace targeted codons with their synonyms.

我們首先將 400 萬個特征的 代碼放在計算機中, 使用查找和替換操作 將目標密碼子替換為其同義詞。

【29】This created our new genome design, which contained more than 18,000 changes with respect to the original genome.

這創(chuàng)造了我們新的基因組設計, 其中包含相對于原始基因組的 18,000 多個變化。

【30】We then asked whether we could build an organism that runs on our synthetic genome design.

然后我們想知道 我們是否可以構建一個 在我們的合成基因組設計上 運行的有機體。

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

我們從短的 DNA 片段開始 構建合成基因組。

【32】These were made by chemistry in a test tube, something that would have been prohibitively expensive to do on this scale just a decade or two ago.

這些是在試管中 通過化學方法制成的, 這在十年或二十年前, 這種規(guī)模的制造成本 高得令人望而卻步。

【33】We then assembled these short pieces of DNA into longer stretches of DNA, which we then used to step-by-step replace all four million bases of the E. coli genome.

然后我們將這些 短 DNA 片段組裝成 更長的 DNA 片段, 然后我們用這些片段逐步替換 大腸桿菌基因組的 所有 400 萬個堿基。

【34】This created the largest synthetic genome ever made.

這創(chuàng)造了有史以來 最大的合成基因組。

【35】And the resulting cell was alive.

由此產(chǎn)生的細胞是活的。

【36】Think about that.

想一想。

【37】We streamlined the genetic code, and yet the cell lived.

我們簡化了遺傳密碼, 但細胞仍然活著。

【38】We can create life with a compressed genetic code.

我們可以用壓縮的遺傳密碼 創(chuàng)造生命。

【39】Now because our organism with a compressed genetic code doesn't use all 64 triplet codons to make proteins, we could remove some of the machinery from the cell that normally reads the near-universal genetic code.

現(xiàn)在,由于我們具有 濃縮遺傳密碼的生物體, 不使用所有 64 個三聯(lián)體的 密碼子來制造蛋白質, 我們可以從細胞中移除一些 通常讀取近乎普遍的 遺傳密碼的機制。

【40】Specifically, we could remove components of the translational machinery, specific tRNAs, that normally read the codons that we've removed from the genome.

具體來說,我們可以移除 轉化體系的成分, 即特定的 tRNAs, 它們通常會讀取我們從基因組中 移除的密碼子。

【41】Now, the key point here is that we've created a cell that no longer reads all the codons in the near-universal genetic code.

現(xiàn)在,這里的關鍵點是我們 已經(jīng)創(chuàng)建了一個細胞, 它不再讀取幾乎普遍的 遺傳密碼中的所有密碼子。

【42】Now viruses infect cells.

現(xiàn)在病毒感染細胞。

【43】These might be the cells of our bodies or single-celled microbes like E.coli.

這些可能是我們身體的細胞 或像大腸桿菌這樣的 單細胞微生物。

【44】They commonly have their own DNA, which uses the near-universal genetic code to encode the proteins necessary to make copies of the virus.

它們通常有自己的 DNA, 它使用近乎通用的遺傳密碼 來編碼復制病毒所需的蛋白質。

【45】But viruses don't have the machinery to read the genetic code in their DNA, and instead they rely on the host cell, the machinery of the host cell, to read the genetic code in their DNA and make copies of the virus.

但是病毒沒有讀取其 DNA 中 遺傳密碼的機制, 而是依靠宿主細胞, 即宿主細胞的機制 來讀取其 DNA 中的遺傳密碼 并復制病毒。

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

正是這些病毒副本 繼續(xù)感染其他細胞。

【47】And this is how viruses spread.

這就是病毒傳播的方式。

【48】But viruses are unable to make copies of themselves in our new organism because our new organism doesn't have the machinery to read all the codons in the DNA of the virus.

但病毒無法在我們的 新生物體中復制自己, 因為我們的新生物體沒有 讀取病毒 DNA 中 所有密碼子的機制。

【49】The code in the DNA used in the virus and the host cell's machinery to read that code are incompatible.

病毒中使用的 DNA 中的代碼 與宿主細胞讀取 該代碼的機制是不兼容的。

【50】Therefore, the virus doesn’t spread in the new organism, and the new organism is resistant to viruses.

因此,病毒不會在新生物體內(nèi)傳播, 而且新生物體對病毒具有抵抗力。

【51】In fact, we showed that our new organism was resistant to a wide range of viruses, suggesting that rewriting the genetic code provides a route to creating broadly virus-resistant life.

事實上,我們證明了我們的新生物體 對多種病毒具有抗性, 這表明重寫遺傳密碼 提供了一條創(chuàng)造 廣泛抗病毒生命的途徑。

【52】By extending the approaches we've developed to other organisms, it may be possible to create virus-resistant crops and animals with important applications in agriculture and beyond.

通過將我們開發(fā)的方法 擴展到其他生物體, 有可能會創(chuàng)造出 抗病毒的作物和動物, 在農(nóng)業(yè)和其他領域有重要的應用。

【53】But our advances also provide a foundation for turning cells into the clean factories of the future.

但我們的進步 也為將細胞轉變?yōu)槲磥淼?清潔工廠奠定了基礎。

【54】How?

如何做呢？

【55】So to explain, let me take another step back to how organisms read their genetic code to make proteins.

所以,為了解釋,讓我再回到 有機體如何讀取其遺傳密碼 來制造蛋白質。

【56】Recall that the order of triplet codons in DNA encodes the order of amino acid building blocks in a protein.

回想一下,DNA 中 三聯(lián)體的密碼子的順序 編碼了蛋白質中 氨基酸結構單元的順序。

【57】And it's the translational machinery of cells that reads the triplet codons and builds the corresponding sequence of amino acids.

是細胞的轉換機制 讀取三聯(lián)體的密碼子 并構建相應的氨基酸序列。

【58】The translational machinery of natural cells -- including ribosomes, aminoacyl-tRNA synthetase enzymes and tRNAs -- is a unique and special system for making proteins in which the 20 common amino acids are strung together in a chain.

天然細胞的轉換機制—— 包括核糖體、 氨酰基-tRNA合成酶和tRNAs—— 是一種用于制造蛋白質的 獨特而特殊的系統(tǒng), 其中 20 種常見的氨基酸 串在一起形成一條鏈。

【59】Now, proteins are amazing, but they're just one example from a vast class of molecules known as polymers, which includes plastics, materials and drugs.

現(xiàn)在,蛋白質很神奇, 但它們只是被稱為 聚合物的一大類分子的一個例子, 其中包括塑料、材料和藥物。

【60】And the polymer or linear polymer is really any molecule in which simpler chemical building blocks are strung together in a chain.

聚合物或線性聚合物 實際上是任何分子 其中更簡單的化學結構單元 串在一起形成鏈。

【61】We wanted to unlock the potential of the translational machinery for making plastics, materials and drugs that simply can't be made in any other way, or that could be made more cleanly and efficiently using engineered versions of the cell's translational machinery.

我們希望釋放出轉化機制的潛力 用于制造塑料、材料和藥物, 這些塑料、材料和藥物 根本無法以任何其他方式制造, 或者可以使用 細胞轉化機制的改造方式 可以更清潔、更有效地實現(xiàn)這一點。

【62】The building blocks for these polymers go well beyond the 20 common amino acids used to make proteins.

這些聚合物的組成部分 遠遠超出了用于制造 蛋白質的 20 種常見氨基酸。

【63】It's been impossible to unlock the potential of the translational machinery for making plastics, materials and drugs for two reasons.

它不可能釋放 用于制造塑料、材料和藥物的 轉化機制的潛力。 由于兩個原因。

【64】First, all 64 triplet codons in natural cells are used for making natural proteins, and there are simply no codons available to encode the synthesis of new polymers.

首先,天然細胞中的所有 64 個三聯(lián)體密碼子 都用于制造天然蛋白質, 而且根本沒有可用于編碼 新聚合物合成的密碼子。

【65】Second, the natural translational machinery specifically uses natural amino acids and simply can't use the chemical building blocks required to make new polymers.

其次,天然的轉換機制 專門使用天然氨基酸, 根本無法使用制造 新聚合物所需的化學構件。

【66】However, a virus-resistant organism doesn't use all 64 triplet codons to make proteins and doesn't contain the machinery to read the codons that have been deleted from its genome.

然而,抗病毒生物體 不會使用所有 64 個三聯(lián)體的 密碼子來制造蛋白質, 并且不包含讀取 已從其基因組中 刪除的密碼子的機制。

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

這個細胞為基因編碼的聚合物合成 提供了起點。

【68】To realize genetically-encoded polymer synthesis in our virus-resistant organism, we added synthetic DNA containing the triplet codons we'd removed from the genome of the cell

為了在我們的抗病毒生物體中 實現(xiàn)基因編碼的聚合物合成, 我們添加了含有 我們從細胞的基因組中移除的 三聯(lián)體密碼子的合成 DNA,

【69】and engineered translational machinery to read these codons and reassign them to new chemical building blocks for new polymers.

并設計了轉化機制來 讀取這些密碼子, 并將它們重新分配到 新的化學構件中,用于新的聚合物。

【70】This system can be programmed to make diverse synthetic polymers.

該系統(tǒng)可以編程 以制造各種合成聚合物。

【71】By changing the order of the triplet codons in the synthetic DNA, we can change the order of the chemical building blocks that we program into the resulting polymer.

通過改變合成 DNA 中 三聯(lián)體密碼子的順序, 我們可以改變我們在生成的聚合物中 編程的化學構件的順序。

【72】And by changing the identity of the engineered translational machinery that we add to the cell, we can change the identity of the chemical building blocks from which we compose the polymer.

通過改變我們添加到細胞中的 設計轉換機制的特性, 我們可以改變我們構成聚合物的 化學構件的特性。

【73】Overall, we've created a cellular factory that we can reliably and predictably program to make synthetic polymers.

總體而言,我們已經(jīng)創(chuàng)建了 一個細胞工廠, 我們可以通過可靠且可預測的編程 來制造合成聚合物。

【74】Using our approach, we've already been able to program cells to make new molecules, including molecules from an important class of drugs known as depsipeptide macrocycles.

使用我們的方法, 我們已經(jīng)能夠對細胞進行編程 以制造新分子, 包括來自被稱為縮肽大環(huán)化合物 一類重要藥物的分子。

【75】Molecules in this class include antibiotics, immunosuppressives and anti-tumor compounds.

此類分子包括抗生素、 免疫抑制劑和抗腫瘤化合物。

【76】We've also been able to program cells to make completely synthetic polymers containing the chemical linkages found in several classes of biodegradable plastics.

我們還能夠對細胞進行編程, 以制造完全合成的聚合物, 其中包含在幾類 可生物降解塑料中發(fā)現(xiàn)的化學連接。

【77】As we build new polymer molecules using our cellular factories, we have the opportunity to consider from the beginning how we might also use engineered biological cells to break these polymers down into their constituent chemical building blocks that could be recycled and used for new encoded polymers.

當我們使用我們的細胞工廠 制造新的聚合物分子時, 我們有機會從一開始就考慮 如何使用改造的生物細胞 來分解這些聚合物, 將其分解為 可以回收的化學成分 并用于新的編碼聚合物。

【78】We envision a circular bioeconomy in which our new genetically-encoded plastics and materials are manufactured and ultimately broken down using low-energy cellular processes, taking advantage of existing bioreactors and fermenters.

我們設想了一種循環(huán)生物經(jīng)濟, 在這種經(jīng)濟中,其中我們的 新基因編碼塑料和材料 是利用現(xiàn)有的生物反應器 和發(fā)酵罐制造出來 并使用低能量細胞過程 最終將其分解。

【79】By taking inspiration from nature and reimagining what life can become, we have the opportunity to build the sustainable industries of the future.

通過從大自然中汲取靈感并重新想象 生命可以變成什么樣子, 我們有機會建立未來的可持續(xù)產(chǎn)業(yè)。

【80】Thank you.

謝謝。

【81】(Applause)