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Alright, let me tell you about building synthetic cells
譯者: Lilian Chiu 審譯者: 易帆 余
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and printing life.
好,讓我來跟各位談談建造合成細胞
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But first, let me tell you a quick story.
以及列印生命。
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On March 31, 2013,
但首先,讓我很快說個故事。
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my team and I received an email from an international health organization,
2013 年 3 月 31 日,
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alerting us that two men died in China
我的團隊和我收到一封電子郵件, 寄件者是一間國際健康組織,
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shortly after contracting the H7N9 bird flu.
內容是警告我們, 在中國有兩個人死亡,
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There were fears of a global pandemic
那是他們染上 H7N9 禽流感之後沒多久的事。
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as the virus started rapidly moving across China.
大家很怕發生全球性的流行,
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Although methods existed to produce a flu vaccine
因為病毒開始在中國快速散播。
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and stop the disease from spreading,
雖然的確有方法可以製造流感疫苗
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at best, it would not be available for at least six months.
並阻止該疾病散播,
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This is because a slow, antiquated flu vaccine manufacturing process
但最好的情況是要等至少 六個月才有疫苗可用。
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developed over 70 years ago was the only option.
這是因為流感疫苗的 製造流程很緩慢、很過時,
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The virus would need to be isolated from infected patients,
是至少 70 年前發明的, 但它卻是唯一的選擇。
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packaged up and then sent to a facility
必須要把病毒和受感染的病人分離,
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where scientists would inject the virus into chicken eggs,
包裝起來,接著送到機構去,
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and incubate those chicken eggs for several weeks
在機構中,科學家會 把病毒注射到雞蛋中,
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in order to prepare the virus for the start of a multistep,
花數週的時間孵那些雞蛋,
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multimonth flu vaccine manufacturing process.
這樣才能將病毒準備好, 開始進行這個有很多步驟、
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My team and I received this email
要花數個月時間的疫苗製造流程。
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because we had just invented a biological printer,
我的團隊和我收到這封電子郵件,
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which would allow for the flu vaccine instructions
是因為我們剛發明了 一台生物列印機,
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to be instantly downloaded from the internet and printed.
有了它,就能夠馬上從網路上
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Drastically speeding up the way in which flu vaccines are made,
下載流感疫苗的說明書, 並將疫苗列印出來。
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and potentially saving thousands of lives.
如此製造流感疫苗就能夠加快許多,
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The biological printer leverages our ability to read and write DNA
很可能可以拯救數千條性命。
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and starts to bring into focus
生物列印機能讓我們 發揮讀寫 DNA 的能力,
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what we like to call biological teleportation.
並讓我們所謂的
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I am a biologist and an engineer who builds stuff out of DNA.
生物電子傳送開始被重視。
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Believe it or not, one of my favorite things to do
我是生物學家及工程師, 我用 DNA 來建造東西。
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is to take DNA apart and put it back together
信不信由你, 我最喜歡做的事情之一,
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so that I can understand better how it works.
就是把 DNA 拆解, 再把它組裝回去,
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I can edit and program DNA to do things, just like coders programing a computer.
這樣我才能更了解它是怎麼運作的。
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But my apps are different.
我可以編輯 DNA、為它寫程式, 就像程式人員為電腦寫程式。
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They create life.
但我的應用程式不同。
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Self-replicating living cells and things like vaccines and therapeutics
它們能創造生命。
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that work in ways that were previously impossible.
自我複製的活細胞, 以及像疫苗及治療法等等,
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Here's National Medal of Science recipient Craig Venter
都能以過去不可能做到的方式運作。
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and Nobel laureate Ham Smith.
這是美國國家科學獎章 得主克萊格凡特,
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These two guys shared a similar vision.
及諾貝爾得主漢彌爾頓史密斯。
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That vision was, because all of the functions and characteristics
他們兩個人有很相似的遠景。
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of all biological entities, including viruses and living cells,
這個遠景就是,
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are written into the code of DNA,
因為所有生物實體的功能和特徵,
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if one can read and write that code of DNA,
包括病毒和活細胞的,
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then they can be reconstructed in a distant location.
全都被寫在 DNA 碼當中,
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This is what we mean by biological teleportation.
如果你能夠讀寫 DNA 碼,
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To prove out this vision,
就可以從遠端重新建造它們。
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Craig and Ham set a goal of creating, for the first time,
我們所謂的生物傳送就是這個意思。
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a synthetic cell, starting from DNA code in the computer.
為了證明這個遠景,
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I mean, come on, as a scientist looking for a job,
克萊格和漢彌爾頓設定了 一個目標,這是第一次
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doing cutting-edge research, it doesn't get any better than this.
合成細胞是從電腦中的 DNA 碼開始創造出來的。
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(Laughter)
我的意思是,拜託, 對一個正在找工作的科學家,
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OK, a genome is a complete set of DNA within an organism.
做最尖端的研究, 沒有什麼比這更好的了。
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Following the Human Genome Project in 2003,
(笑聲)
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which was an international effort to identify
好,基因組是在有機體當中 完整的一組 DNA。
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the complete genetic blueprint of a human being,
2003 年有一個人類基因組計劃, 它是一項國際合作,
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a genomics revolution happened.
要找出人類的完整基因藍圖, 而在這計畫之後,
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Scientists started mastering the techniques for reading DNA.
發生了一次基因組學的革命。
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In order to determine the order of the As, Cs, Ts and Gs
科學家開始精通讀 DNA 的技巧,
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within an organism.
目的是要判斷一個有機體 當中 A、C、T,
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But my job was far different.
和 G 的順序。
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I needed to master the techniques for writing DNA.
但我的工作非常不同。
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Like an author of a book,
我得要精通寫 DNA 的技巧。
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this started out as writing short sentences,
就像一本書的作者,
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or sequences of DNA code,
一開始是寫簡短的句子,
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but this soon turned into writing paragraphs
或是 DNA 碼的序列,
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and then full-on novels of DNA code,
但很快就會變成要寫段落,
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to make important biological instructions for proteins and living cells.
再來就是要寫 DNA 碼的整本書了,
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Living cells are nature's most efficient machines at making new products,
也就是要針對蛋白質和活細胞, 編寫出重要的生物說明書。
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accounting for the production
就製造新產品來說,活細胞 是大自然中最有效率的機器,
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of 25 percent of the total pharmaceutical market,
產量就佔了
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which is billions of dollars.
整個藥品市場的 25%,
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We knew that writing DNA would drive this bioeconomy even more,
也就是數十億美元。
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once cells could be programmed just like computers.
我們知道一旦寫細胞 DNA 程式 能夠像寫電腦程式一樣,
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We also knew that writing DNA would enable biological teleportation ...
就能再進一步推動這種生物經濟。
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the printing of defined, biological material,
我們也知道,能寫 DNA 就能讓生物傳送成真……
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starting from DNA code.
將定義好的生物材料列印出來,
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As a step toward bringing these promises to fruition,
從 DNA 碼開始。
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our team set out to create, for the first time,
為了朝實現這個夢想踏出一步,
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a synthetic bacterial cell,
我們的團隊打算 做一件史無前例的事:
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starting from DNA code in the computer.
從電腦中的 DNA 碼開始,
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Synthetic DNA is a commodity.
創造出合成細菌細胞。
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You can order very short pieces of DNA from a number of companies,
合成 DNA 是一種商品。
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and they will start from these four bottles of chemicals that make up DNA,
你可以向好幾間公司 訂購非常短的 DNA,
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G, A, T and C,
它們會從製造 DNA 的 這四瓶化學物質開始:
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and they will build those very short pieces of DNA for you.
G、A、T,和 C,
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Over the past 15 years or so,
它們會為你建造出 那些非常短的 DNA。
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my teams have been developing the technology
在過去 15 年左右,
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for stitching together those short pieces of DNA
我的團隊一直在開發一項技術,
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into complete bacterial genomes.
將那些非常短的 DNA 組合在一起,
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The largest genome that we constructed contained over one million letters.
成為完整的細菌基因組。
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Which is more than twice the size of your average novel,
我們建造出來最大的基因組 內容超過一百萬個字母。
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and we had to put every single one of those letters in the correct order,
這是一般小說長度的兩倍,
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without a single typo.
且我們把所有那些字母 通通都排成正確的順序,
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We were able to accomplish this by developing a procedure
沒有任何打字錯誤。
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that I tried to call the "one-step isothermal in vitro recombination method."
我們之所以能完成它, 是因為開發出了一種程序,
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(Laughter)
我想稱它為「一步驟 等溫室管內重新組合法」。
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But, surprisingly, the science community didn't like this technically accurate name
(笑聲)
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and decided to call it Gibson Assembly.
但意外的是,科學界並不喜歡 這種在技術面上很精確的命名,
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Gibson Assembly is now the gold standard tool,
決定要叫它「吉布森組合」。
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used in laboratories around the world
吉布森組合現在是黃金標準工具,
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for building short and long pieces of DNA.
全世界的實驗室都在使用它,
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(Applause)
用來建造短的及長的 DNA。
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Once we chemically synthesized the complete bacterial genome,
(掌聲)
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our next challenge was to find a way
一旦我們以化學方式合成了 完整的細菌基因組,
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to convert it into a free-living, self-replicating cell.
我們的下一個挑戰是要想辦法
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Our approach was to think of the genome as the operating system of the cell,
將它轉換為能獨立生存、 自我複製的細胞。
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with the cell containing the hardware necessary to boot up the genome.
我們的方法是把基因組 當作細胞的作業系統,
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Through a lot of trial and error,
細胞內含有必要的硬體, 可以啟動基因組。
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we developed a procedure where we could reprogram cells
經過許多次的反複試驗,
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and even convert one bacterial species into another,
我們發展出了一種程序, 讓我們能為細胞重新寫程式,
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by replacing the genome of one cell with that of another.
甚至將一種細菌轉換成另一種,
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This genome transplantation technology then paved the way
做法就是將一個細胞的基因組 置換成另一個細胞的基因組。
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for the booting-up of genomes written by scientists
這種基因組移植技術奠定了基礎,
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and not by Mother Nature.
讓科學家,而非大自然,
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In 2010, all of the technologies
所寫的基因組能夠啟動。
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that we had been developing for reading and writing DNA
2010 年,我們為了
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all came together when we announced the creation
讀寫 DNA 所發展的所有技術
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of the first synthetic cell,
通通整合在一起, 那時我們宣佈創造出了
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which of course, we called Synthia.
第一個合成細胞,
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(Laughter)
當然,我們稱它為辛西雅。 (註:發音近似「合成」。)
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Ever since the first bacterial genome was sequenced, back in 1995,
(笑聲)
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thousands more whole bacterial genomes have been sequenced and stored
從 1995 年成功完成 第一次基因組定序之後,
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in computer databases.
有數千組細菌基因組被定序 並儲存在電腦資料庫中。
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Our synthetic cell work was the proof of concept
我們的合成細胞成果 證明了一個概念,
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that we could reverse this process:
那就是我們能反轉這個過程:
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pull a complete bacterial genome sequence out of the computer
從電腦中拉出一組 完整的細菌基因組列,
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and convert that information into a free-living, self-replicating cell,
將那資訊轉換成為獨立生存、 自我複製的細胞,
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with all of the expected characteristics of the species that we constructed.
且具有我們所建立之物種 應該要有的所有特徵。
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Now I can understand why there may be concerns
我可以了解為什麼有人會擔心
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about the safety of this level of genetic manipulation.
這種程度的基因操控是否安全。
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While the technology has the potential for great societal benefit,
雖然這項技術可能可以 為社會帶來很大的益處,
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it also has the potential for doing harm.
它也有可能會造成傷害。
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With this in mind, even before carrying out the very first experiment,
我們的團隊牢記著這一點, 在開始進行最初一次實驗時,
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our team started to work with the public and the government
我們就開始和大眾以及政府合作,
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to find solutions together
一起想辦法以負責的方式
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to responsibly develop and regulate this new technology.
來發展和規範這項新技術。
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One of the outcomes from those discussions was to screen every customer
其中一項得出的討論結果 是要審查每一位客戶
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and every customer's DNA synthesis orders,
和每一位客戶的 DNA 合成順序,
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to make sure that pathogens or toxins are not being made by bad guys,
以確保不會有病原體 或毒物被壞人製造出來,
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or accidentally by scientists.
或不小心被科學家製造出來。
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All suspicious orders are reported to the FBI
所有可疑的順序都要 回報給聯邦調查局
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and other relevant law-enforcement agencies.
和其他相關的執法機關。
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Synthetic cell technologies will power the next industrial revolution
合成細胞技術能夠 驅動下一波的工業革命,
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and transform industries and economies
並讓產業和經濟體轉型,
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in ways that address global sustainability challenges.
進而解決全球永續性問題的挑戰。
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The possibilities are endless.
可能性是無盡的。
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I mean, you can think of clothes
各位可以想想衣服,
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constructed form renewable biobased sources,
從可再生的生物來源建造出來,
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cars running on biofuel from engineered microbes,
工程微生物所產生的生物燃料 可以供應給汽車使用,
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plastics made from biodegradable polymers
用可生物降解的聚合物來製造塑膠,
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and customized therapies, printed at a patient's bedside.
還有客製化的治療, 直接在病人的病床邊列印出來。
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The massive efforts to create synthetic cells
我們投入大量心力在創造合成細胞,
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have made us world leaders at writing DNA.
也因此我們在寫 DNA 這方面領先全世界。
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Throughout the process, we found ways to write DNA faster,
在這個過程中,我們發現了 可以更快速寫 DNA 的方式,
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more accurately and more reliably.
這個方式也更正確、可靠。
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Because of the robustness of these technologies,
因為這些技術很健全,
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we found that we could readily automate the processes
我們發現,我們已經 可以將過程給自動化,
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and move the laboratory workflows out of the scientist's hands
科學家不用再處理 實驗室的工作流程,
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and onto a machine.
交給機器即可。
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In 2013, we built the first DNA printer.
2013 年,我們打造了 第一台 DNA 列印機。
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We call it the BioXp.
我們把它取名叫 BioXp。
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And it has been absolutely essential in writing DNA
它對於寫 DNA 來說非常重要,
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across a number of applications
我的團隊和世界各地的研究者
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my team and researchers around the world are working on.
在研究的數種應用都很需要它。
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It was shortly after we built the BioXp
在我們打造出 BioXp 之後沒多久,
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that we received that email about the H7N9 bird flu scare in China.
我們就收到了那封關於 中國 H7N9 禽流感的電子郵件。
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A team of Chinese scientists had already isolated the virus,
中國的一個科學家團隊 已經將病毒分離出來,
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sequenced its DNA and uploaded the DNA sequence to the internet.
將它的 DNA 定序, 並把該 DNA 序列上傳到網路上。
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At the request of the US government, we downloaded the DNA sequence
在美國政府的請求下, 我們下載了該 DNA 序列,
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and in less than 12 hours, we printed it on the BioXp.
不到 12 小時,我們 就用 BioXp 列印了它。
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Our collaborators at Novartis
我們在諾華的共同研究者
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then quickly started turning that synthetic DNA into a flu vaccine.
很快就開始將那合成 DNA 轉為流感疫苗。
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Meanwhile, the CDC, using technology dating back to the 1940s,
同時,疾病防治中心用的是 40 年代發展的技術,
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was still waiting for the virus to arrive from China
他們還在等待 從中國送過來的病毒,
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so that they could begin their egg-based approach.
收到之後他們才能開始 採用雞蛋培育的那種方式。
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For the first time, we had a flu vaccine developed ahead of time
這是第一次,我們針對 一種可能很危險的新菌株
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for a new and potentially dangerous strain,
提前開發出了流感疫苗,
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and the US government ordered a stockpile.
且美國政府訂購了一堆來儲備。
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(Applause)
(掌聲)
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This was when I began to appreciate, more than ever,
從這個時候開始,我比以前更加欣賞
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the power of biological teleportation.
生物電子傳送的力量。
-
(Laughter)
(笑聲)
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Naturally, with this in mind,
很自然地,因為這一點,
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we started to build a biological teleporter.
我們便開始建造生物電子傳送機。
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We call it the DBC.
我們稱它為 DBC,
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That's short for digital-to-biological converter.
是「數位轉為生物之轉換器」的縮寫。
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Unlike the BioXp,
它和 BioXp 不同,
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which starts from pre-manufactured short pieces of DNA,
BioXp 是從預先製造的 短 DNA 開始,
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the DBC starts from digitized DNA code
而 DBC 是從數位化的 DNA 碼開始,
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and converts that DNA code into biological entities,
並將該 DNA 碼轉換為生物實體,
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such as DNA, RNA, proteins or even viruses.
比如 DNA、RNA、 蛋白質,或甚至病毒。
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You can think of the BioXp as a DVD player,
可以把 BioXp 想成是 一台 DVD 播放機,
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requiring a physical DVD to be inserted,
需要放入實體的 DVD,
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whereas the DBC is Netflix.
而 DBC 就是網飛。
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To build the DBC,
為了打造 DBC,
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my team of scientists worked with software and instrumentation engineers
我的科學家團隊和 軟體及儀表工程師合作,
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to collapse multiple laboratory workflows,
將多種實驗室工作流程整合起來,
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all in a single box.
通通放在單一個盒子中。
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This included software algorithms to predict what DNA to build,
這內容包括了用來預測要建造 哪種 DNA 的軟體演算法、
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chemistry to link the G, A, T and C building blocks of DNA into short pieces,
將 DNA 的 G、A、T 及 C 積木 連結起來變成短 DNA 的化學、
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Gibson Assembly to stitch together those short pieces into much longer ones,
將這些短 DNA 組合成 更長的 DNA 的吉布森組合,
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and biology to convert the DNA into other biological entities,
及將 DNA 轉換成其他生物實體 (如蛋白質)的生物學。
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such as proteins.
這是它的原型。
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This is the prototype.
雖然它長得不好看,但很有效。
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Although it wasn't pretty, it was effective.
它能製造出治療用的藥物和疫苗。
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It made therapeutic drugs and vaccines.
以前要花數個星期 甚至數個月的實驗室工作流程,
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And laboratory workflows that once took weeks or months
現在只要一到兩天就可以完成。
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could now be carried out in just one to two days.
且過程是完全不需要人類動手的,
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And that's all without any human intervention
只要接收到電子郵件就可以啟動,
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and simply activated by the receipt of an email
從世界上任何地方發信都可以。
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which could be sent from anywhere in the world.
我們會把 DBC 比喻成傳真機。
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We like to compare the DBC to fax machines.
不過傳真機接收的是影像和文件,
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But whereas fax machines received images and documents,
而 DBC 接收的是生物材料。
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the DBC receives biological materials.
想想看傳真機是如何演化的。
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Now, consider how fax machines have evolved.
和現今的傳真機相比,
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The prototype of the 1840s is unrecognizable,
1840 年代的原型機大家都不認得了。
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compared with the fax machines of today.
八○年代,大部分的人 仍然不知道傳真機是什麼,
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In the 1980s, most people still didn't know what a fax machine was,
就算知道,
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and if they did,
他們也很難理解那個概念,
-
it was difficult for them to grasp the concept
無法想像如何能從世界的另一端 立即重新製造出一張影像。
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of instantly reproducing an image on the other side of the world.
但現今,傳真機所有的功能 都被整合到我們的智慧手機中,
-
But nowadays, everything that a fax machine does
我們還視快速交換 數位資訊為理所當然。
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is integrated on our smart phones,
現在我們的 DBC 是這樣的。
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and of course, we take this rapid exchange of digital information for granted.
我們想像 DBC 和傳真機 用類似的方式演化。
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Here's what our DBC looks like today.
我們正在努力 把這台儀器的尺寸縮減,
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We imagine the DBC evolving in similar ways as fax machines have.
我們也在努力讓背後要用到的技術
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We're working to reduce the size of the instrument,
更可靠、更便宜、更快速且更精確。
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and we're working to make the underlying technology
在合成 DNA 時, 精確性是極度重要的,
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more reliable, cheaper, faster and more accurate.
因為只要有一個 DNA 字母不一樣,
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Accuracy is extremely important when synthesizing DNA,
可能就是藥品是否有效的差別,
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because a single change to a DNA letter
或合成細胞是生是死的差別。
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could mean the difference between a medicine working or not
若要針對從 DNA 開始的藥品 進行分散製造,
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or synthetic cell being alive or dead.
DBC 是很有用的。
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The DBC will be useful for the distributed manufacturing
世界上的每一間醫院 都能用一台 DBC
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of medicine starting from DNA.
直接在病人的病床邊為他們 列印出個人化的藥品。
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Every hospital in the world could use a DBC
我甚至可以想像有一天, 人類的日常會變成是
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for printing personalized medicines for a patient at their bedside.
每個人的家中電腦或智慧手機 都和一台 DBC 連結在一起,
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I can even imagine a day when it's routine for people to have a DBC
可以直接下載他們的處方,
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to connect to their home computer or smart phone
比如胰島素或抗生素治療。
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as a means to download their prescriptions,
DBC 還有一個很大的價值, 就是放在世界各地的戰略地區,
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such as insulin or antibody therapies.
對疾病的爆發能做出快速應變。
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The DBC will also be valuable when placed in strategic areas around the world,
比如,喬治亞州 亞特蘭大的疾病防治中心