Alright, let me tell you about building synthetic cells and printing life. But first, let me tell you a quick story. On March 31, 2013, my team and I received an email from an international health organization, alerting us that two men died in China shortly after contracting the H7N9 bird flu. There were fears of a global pandemic as the virus started rapidly moving across China. Although methods existed to produce a flu vaccine and stop the disease from spreading, at best, it would not be available for at least six months. This is because a slow, antiquated flu vaccine manufacturing process developed over 70 years ago was the only option.
好,讓我來跟各位談談建造合成細胞 以及列印生命。 但首先,讓我很快說個故事。 2013 年 3 月 31 日, 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, 內容是警告我們, 在中國有兩個人死亡, 那是他們染上 H7N9 禽流感之後沒多久的事。 大家很怕發生全球性的流行, 因為病毒開始在中國快速散播。 雖然的確有方法可以製造流感疫苗 並阻止該疾病散播, 但最好的情況是要等至少 六個月才有疫苗可用。 這是因為流感疫苗的 製造流程很緩慢、很過時, 是至少 70 年前發明的, 但它卻是唯一的選擇。
The virus would need to be isolated from infected patients, packaged up and then sent to a facility where scientists would inject the virus into chicken eggs, and incubate those chicken eggs for several weeks in order to prepare the virus for the start of a multistep, multimonth flu vaccine manufacturing process. My team and I received this email because we had just invented a biological printer, which would allow for the flu vaccine instructions to be instantly downloaded from the internet and printed. Drastically speeding up the way in which flu vaccines are made, and potentially saving thousands of lives.
必須要把病毒和受感染的病人分離, 包裝起來,接著送到機構去, 在機構中,科學家會 把病毒注射到雞蛋中, 花數週的時間孵那些雞蛋, 這樣才能將病毒準備好, 開始進行這個有很多步驟、 要花數個月時間的疫苗製造流程。 我的團隊和我收到這封電子郵件, 是因為我們剛發明了 一台生物列印機, 有了它,就能夠馬上從網路上 下載流感疫苗的說明書, 並將疫苗列印出來。 如此製造流感疫苗就能夠加快許多, 很可能可以拯救數千條性命。
The biological printer leverages our ability to read and write DNA and starts to bring into focus what we like to call biological teleportation. I am a biologist and an engineer who builds stuff out of DNA. Believe it or not, one of my favorite things to do is to take DNA apart and put it back together so that I can understand better how it works. I can edit and program DNA to do things, just like coders programing a computer. But my apps are different. They create life. Self-replicating living cells and things like vaccines and therapeutics that work in ways that were previously impossible.
生物列印機能讓我們 發揮讀寫 DNA 的能力, 並讓我們所謂的 生物電子傳送開始被重視。 我是生物學家及工程師, 我用 DNA 來建造東西。 信不信由你, 我最喜歡做的事情之一, 就是把 DNA 拆解, 再把它組裝回去, 這樣我才能更了解它是怎麼運作的。 我可以編輯 DNA、為它寫程式, 就像程式人員為電腦寫程式。 但我的應用程式不同。 它們能創造生命。 自我複製的活細胞, 以及像疫苗及治療法等等, 都能以過去不可能做到的方式運作。
Here's National Medal of Science recipient Craig Venter and Nobel laureate Ham Smith. These two guys shared a similar vision. That vision was, because all of the functions and characteristics of all biological entities, including viruses and living cells, are written into the code of DNA, if one can read and write that code of DNA, then they can be reconstructed in a distant location. This is what we mean by biological teleportation. To prove out this vision, Craig and Ham set a goal of creating, for the first time, a synthetic cell, starting from DNA code in the computer. I mean, come on, as a scientist looking for a job, doing cutting-edge research, it doesn't get any better than this.
這是美國國家科學獎章 得主克萊格凡特, 及諾貝爾得主漢彌爾頓史密斯。 他們兩個人有很相似的遠景。 這個遠景就是, 因為所有生物實體的功能和特徵, 包括病毒和活細胞的, 全都被寫在 DNA 碼當中, 如果你能夠讀寫 DNA 碼, 就可以從遠端重新建造它們。 我們所謂的生物傳送就是這個意思。 為了證明這個遠景, 克萊格和漢彌爾頓設定了 一個目標,這是第一次 合成細胞是從電腦中的 DNA 碼開始創造出來的。 我的意思是,拜託, 對一個正在找工作的科學家, 做最尖端的研究, 沒有什麼比這更好的了。
(Laughter)
(笑聲)
OK, a genome is a complete set of DNA within an organism. Following the Human Genome Project in 2003, which was an international effort to identify the complete genetic blueprint of a human being, a genomics revolution happened. Scientists started mastering the techniques for reading DNA. In order to determine the order of the As, Cs, Ts and Gs within an organism. But my job was far different. I needed to master the techniques for writing DNA. Like an author of a book, this started out as writing short sentences, or sequences of DNA code, but this soon turned into writing paragraphs and then full-on novels of DNA code, to make important biological instructions for proteins and living cells. Living cells are nature's most efficient machines at making new products, accounting for the production of 25 percent of the total pharmaceutical market, which is billions of dollars.
好,基因組是在有機體當中 完整的一組 DNA。 2003 年有一個人類基因組計劃, 它是一項國際合作, 要找出人類的完整基因藍圖, 而在這計畫之後, 發生了一次基因組學的革命。 科學家開始精通讀 DNA 的技巧, 目的是要判斷一個有機體 當中 A、C、T, 和 G 的順序。 但我的工作非常不同。 我得要精通寫 DNA 的技巧。 就像一本書的作者, 一開始是寫簡短的句子, 或是 DNA 碼的序列, 但很快就會變成要寫段落, 再來就是要寫 DNA 碼的整本書了, 也就是要針對蛋白質和活細胞, 編寫出重要的生物說明書。 就製造新產品來說,活細胞 是大自然中最有效率的機器, 產量就佔了 整個藥品市場的 25%, 也就是數十億美元。
We knew that writing DNA would drive this bioeconomy even more, once cells could be programmed just like computers. We also knew that writing DNA would enable biological teleportation ... the printing of defined, biological material, starting from DNA code. As a step toward bringing these promises to fruition, our team set out to create, for the first time, a synthetic bacterial cell, starting from DNA code in the computer. Synthetic DNA is a commodity. You can order very short pieces of DNA from a number of companies, and they will start from these four bottles of chemicals that make up DNA, G, A, T and C, and they will build those very short pieces of DNA for you.
我們知道一旦寫細胞 DNA 程式 能夠像寫電腦程式一樣, 就能再進一步推動這種生物經濟。 我們也知道,能寫 DNA 就能讓生物傳送成真…… 將定義好的生物材料列印出來, 從 DNA 碼開始。 為了朝實現這個夢想踏出一步, 我們的團隊打算 做一件史無前例的事: 從電腦中的 DNA 碼開始, 創造出合成細菌細胞。 合成 DNA 是一種商品。 你可以向好幾間公司 訂購非常短的 DNA, 它們會從製造 DNA 的 這四瓶化學物質開始: G、A、T,和 C, 它們會為你建造出 那些非常短的 DNA。
Over the past 15 years or so, my teams have been developing the technology for stitching together those short pieces of DNA into complete bacterial genomes. The largest genome that we constructed contained over one million letters. Which is more than twice the size of your average novel, and we had to put every single one of those letters in the correct order, without a single typo. We were able to accomplish this by developing a procedure that I tried to call the "one-step isothermal in vitro recombination method."
在過去 15 年左右, 我的團隊一直在開發一項技術, 將那些非常短的 DNA 組合在一起, 成為完整的細菌基因組。 我們建造出來最大的基因組 內容超過一百萬個字母。 這是一般小說長度的兩倍, 且我們把所有那些字母 通通都排成正確的順序, 沒有任何打字錯誤。 我們之所以能完成它, 是因為開發出了一種程序, 我想稱它為「一步驟 等溫室管內重新組合法」。
(Laughter)
(笑聲)
But, surprisingly, the science community didn't like this technically accurate name and decided to call it Gibson Assembly. Gibson Assembly is now the gold standard tool, used in laboratories around the world for building short and long pieces of DNA.
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, 決定要叫它「吉布森組合」。 吉布森組合現在是黃金標準工具, 全世界的實驗室都在使用它, 用來建造短的及長的 DNA。
(Applause)
(掌聲)
Once we chemically synthesized the complete bacterial genome, our next challenge was to find a way to convert it into a free-living, self-replicating cell. Our approach was to think of the genome as the operating system of the cell, with the cell containing the hardware necessary to boot up the genome. Through a lot of trial and error, we developed a procedure where we could reprogram cells and even convert one bacterial species into another, by replacing the genome of one cell with that of another. This genome transplantation technology then paved the way for the booting-up of genomes written by scientists and not by Mother Nature. In 2010, all of the technologies that we had been developing for reading and writing DNA all came together when we announced the creation of the first synthetic cell, which of course, we called Synthia.
一旦我們以化學方式合成了 完整的細菌基因組, 我們的下一個挑戰是要想辦法 將它轉換為能獨立生存、 自我複製的細胞。 我們的方法是把基因組 當作細胞的作業系統, 細胞內含有必要的硬體, 可以啟動基因組。 經過許多次的反複試驗, 我們發展出了一種程序, 讓我們能為細胞重新寫程式, 甚至將一種細菌轉換成另一種, 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。 這種基因組移植技術奠定了基礎, 讓科學家,而非大自然, 所寫的基因組能夠啟動。 2010 年,我們為了 讀寫 DNA 所發展的所有技術 通通整合在一起, 那時我們宣佈創造出了 第一個合成細胞, 當然,我們稱它為辛西雅。 (註:發音近似「合成」。)
(Laughter)
(笑聲)
Ever since the first bacterial genome was sequenced, back in 1995, thousands more whole bacterial genomes have been sequenced and stored in computer databases. Our synthetic cell work was the proof of concept that we could reverse this process: pull a complete bacterial genome sequence out of the computer and convert that information into a free-living, self-replicating cell, with all of the expected characteristics of the species that we constructed.
從 1995 年成功完成 第一次基因組定序之後, 有數千組細菌基因組被定序 並儲存在電腦資料庫中。 我們的合成細胞成果 證明了一個概念, 那就是我們能反轉這個過程: 從電腦中拉出一組 完整的細菌基因組列, 將那資訊轉換成為獨立生存、 自我複製的細胞, 且具有我們所建立之物種 應該要有的所有特徵。
Now I can understand why there may be concerns about the safety of this level of genetic manipulation. While the technology has the potential for great societal benefit, it also has the potential for doing harm. With this in mind, even before carrying out the very first experiment, our team started to work with the public and the government to find solutions together to responsibly develop and regulate this new technology. One of the outcomes from those discussions was to screen every customer and every customer's DNA synthesis orders, to make sure that pathogens or toxins are not being made by bad guys, or accidentally by scientists. All suspicious orders are reported to the FBI and other relevant law-enforcement agencies.
我可以了解為什麼有人會擔心 這種程度的基因操控是否安全。 雖然這項技術可能可以 為社會帶來很大的益處, 它也有可能會造成傷害。 我們的團隊牢記著這一點, 在開始進行最初一次實驗時, 我們就開始和大眾以及政府合作, 一起想辦法以負責的方式 來發展和規範這項新技術。 其中一項得出的討論結果 是要審查每一位客戶 和每一位客戶的 DNA 合成順序, 以確保不會有病原體 或毒物被壞人製造出來, 或不小心被科學家製造出來。 所有可疑的順序都要 回報給聯邦調查局 和其他相關的執法機關。
Synthetic cell technologies will power the next industrial revolution and transform industries and economies in ways that address global sustainability challenges. The possibilities are endless. I mean, you can think of clothes constructed form renewable biobased sources, cars running on biofuel from engineered microbes, plastics made from biodegradable polymers and customized therapies, printed at a patient's bedside. The massive efforts to create synthetic cells have made us world leaders at writing DNA. Throughout the process, we found ways to write DNA faster, more accurately and more reliably.
合成細胞技術能夠 驅動下一波的工業革命, 並讓產業和經濟體轉型, 進而解決全球永續性問題的挑戰。 可能性是無盡的。 各位可以想想衣服, 從可再生的生物來源建造出來, 工程微生物所產生的生物燃料 可以供應給汽車使用, 用可生物降解的聚合物來製造塑膠, 還有客製化的治療, 直接在病人的病床邊列印出來。 我們投入大量心力在創造合成細胞, 也因此我們在寫 DNA 這方面領先全世界。 在這個過程中,我們發現了 可以更快速寫 DNA 的方式, 這個方式也更正確、可靠。
Because of the robustness of these technologies, we found that we could readily automate the processes and move the laboratory workflows out of the scientist's hands and onto a machine. In 2013, we built the first DNA printer. We call it the BioXp. And it has been absolutely essential in writing DNA across a number of applications my team and researchers around the world are working on.
因為這些技術很健全, 我們發現,我們已經 可以將過程給自動化, 科學家不用再處理 實驗室的工作流程, 交給機器即可。 2013 年,我們打造了 第一台 DNA 列印機。 我們把它取名叫 BioXp。 它對於寫 DNA 來說非常重要, 我的團隊和世界各地的研究者 在研究的數種應用都很需要它。
It was shortly after we built the BioXp that we received that email about the H7N9 bird flu scare in China. A team of Chinese scientists had already isolated the virus, sequenced its DNA and uploaded the DNA sequence to the internet. At the request of the US government, we downloaded the DNA sequence and in less than 12 hours, we printed it on the BioXp. Our collaborators at Novartis then quickly started turning that synthetic DNA into a flu vaccine. Meanwhile, the CDC, using technology dating back to the 1940s, was still waiting for the virus to arrive from China so that they could begin their egg-based approach. For the first time, we had a flu vaccine developed ahead of time for a new and potentially dangerous strain, and the US government ordered a stockpile.
在我們打造出 BioXp 之後沒多久, 我們就收到了那封關於 中國 H7N9 禽流感的電子郵件。 中國的一個科學家團隊 已經將病毒分離出來, 將它的 DNA 定序, 並把該 DNA 序列上傳到網路上。 在美國政府的請求下, 我們下載了該 DNA 序列, 不到 12 小時,我們 就用 BioXp 列印了它。 我們在諾華的共同研究者 很快就開始將那合成 DNA 轉為流感疫苗。 同時,疾病防治中心用的是 40 年代發展的技術, 他們還在等待 從中國送過來的病毒, 收到之後他們才能開始 採用雞蛋培育的那種方式。 這是第一次,我們針對 一種可能很危險的新菌株 提前開發出了流感疫苗, 且美國政府訂購了一堆來儲備。
(Applause)
(掌聲)
This was when I began to appreciate, more than ever, the power of biological teleportation.
從這個時候開始,我比以前更加欣賞 生物電子傳送的力量。
(Laughter)
(笑聲)
Naturally, with this in mind, we started to build a biological teleporter. We call it the DBC. That's short for digital-to-biological converter. Unlike the BioXp, which starts from pre-manufactured short pieces of DNA, the DBC starts from digitized DNA code and converts that DNA code into biological entities, such as DNA, RNA, proteins or even viruses. You can think of the BioXp as a DVD player, requiring a physical DVD to be inserted, whereas the DBC is Netflix. To build the DBC, my team of scientists worked with software and instrumentation engineers to collapse multiple laboratory workflows, all in a single box. This included software algorithms to predict what DNA to build, chemistry to link the G, A, T and C building blocks of DNA into short pieces, Gibson Assembly to stitch together those short pieces into much longer ones, and biology to convert the DNA into other biological entities, such as proteins.
很自然地,因為這一點, 我們便開始建造生物電子傳送機。 我們稱它為 DBC, 是「數位轉為生物之轉換器」的縮寫。 它和 BioXp 不同, BioXp 是從預先製造的 短 DNA 開始, 而 DBC 是從數位化的 DNA 碼開始, 並將該 DNA 碼轉換為生物實體, 比如 DNA、RNA、 蛋白質,或甚至病毒。 可以把 BioXp 想成是 一台 DVD 播放機, 需要放入實體的 DVD, 而 DBC 就是網飛。 為了打造 DBC, 我的科學家團隊和 軟體及儀表工程師合作, 將多種實驗室工作流程整合起來, 通通放在單一個盒子中。 這內容包括了用來預測要建造 哪種 DNA 的軟體演算法、 將 DNA 的 G、A、T 及 C 積木 連結起來變成短 DNA 的化學、 將這些短 DNA 組合成 更長的 DNA 的吉布森組合, 及將 DNA 轉換成其他生物實體 (如蛋白質)的生物學。
This is the prototype. Although it wasn't pretty, it was effective. It made therapeutic drugs and vaccines. And laboratory workflows that once took weeks or months could now be carried out in just one to two days. And that's all without any human intervention and simply activated by the receipt of an email which could be sent from anywhere in the world. We like to compare the DBC to fax machines. But whereas fax machines received images and documents, the DBC receives biological materials. Now, consider how fax machines have evolved. The prototype of the 1840s is unrecognizable, compared with the fax machines of today. In the 1980s, most people still didn't know what a fax machine was, and if they did, it was difficult for them to grasp the concept of instantly reproducing an image on the other side of the world. But nowadays, everything that a fax machine does is integrated on our smart phones, and of course, we take this rapid exchange of digital information for granted.
這是它的原型。 雖然它長得不好看,但很有效。 它能製造出治療用的藥物和疫苗。 以前要花數個星期 甚至數個月的實驗室工作流程, 現在只要一到兩天就可以完成。 且過程是完全不需要人類動手的, 只要接收到電子郵件就可以啟動, 從世界上任何地方發信都可以。 我們會把 DBC 比喻成傳真機。 不過傳真機接收的是影像和文件, 而 DBC 接收的是生物材料。 想想看傳真機是如何演化的。 和現今的傳真機相比, 1840 年代的原型機大家都不認得了。 八○年代,大部分的人 仍然不知道傳真機是什麼, 就算知道, 他們也很難理解那個概念, 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。 但現今,傳真機所有的功能 都被整合到我們的智慧手機中, 我們還視快速交換 數位資訊為理所當然。
Here's what our DBC looks like today. We imagine the DBC evolving in similar ways as fax machines have. We're working to reduce the size of the instrument, and we're working to make the underlying technology more reliable, cheaper, faster and more accurate. Accuracy is extremely important when synthesizing DNA, because a single change to a DNA letter could mean the difference between a medicine working or not or synthetic cell being alive or dead.
現在我們的 DBC 是這樣的。 我們想像 DBC 和傳真機 用類似的方式演化。 我們正在努力 把這台儀器的尺寸縮減, 我們也在努力讓背後要用到的技術 更可靠、更便宜、更快速且更精確。 在合成 DNA 時, 精確性是極度重要的, 因為只要有一個 DNA 字母不一樣, 可能就是藥品是否有效的差別, 或合成細胞是生是死的差別。
The DBC will be useful for the distributed manufacturing of medicine starting from DNA. Every hospital in the world could use a DBC for printing personalized medicines for a patient at their bedside. I can even imagine a day when it's routine for people to have a DBC to connect to their home computer or smart phone as a means to download their prescriptions, such as insulin or antibody therapies. The DBC will also be valuable when placed in strategic areas around the world, for rapid response to disease outbreaks. For example, the CDC in Atlanta, Georgia could send flu vaccine instructions to a DBC on the other side of the world, where the flu vaccine is manufactured right on the front lines. That flu vaccine could even be specifically tailored to the flu strain that's circulating in that local area. Sending vaccines around in a digital file, rather than stockpiling those same vaccines and shipping them out, promises to save thousands of lives.
若要針對從 DNA 開始的藥品 進行分散製造, DBC 是很有用的。 世界上的每一間醫院 都能用一台 DBC 直接在病人的病床邊為他們 列印出個人化的藥品。 我甚至可以想像有一天, 人類的日常會變成是 每個人的家中電腦或智慧手機 都和一台 DBC 連結在一起, 可以直接下載他們的處方, 比如胰島素或抗生素治療。 DBC 還有一個很大的價值, 就是放在世界各地的戰略地區, 對疾病的爆發能做出快速應變。 比如,喬治亞州 亞特蘭大的疾病防治中心 就可以把流感疫苗指示 發送給世界另一端的 DBC, 在另一端,就可以直接在最前線 把流感疫苗製造出來。 甚至可以針對當地流行的流感菌株 來量身打造流感疫苗。 以數位檔案的形式把疫苗送到各地, 而不是貯存一堆同樣的疫苗 再將它們運送出去, 這種新方式有望拯救許多條人命。
Of course, the applications go as far as the imagination goes. It's not hard to imagine placing a DBC on another planet. Scientists on Earth could then send the digital instructions to that DBC to make new medicines or to make synthetic organisms that produce oxygen, food, fuel or building materials, as a means for making the planet more habitable for humans.
當然,想像有多廣,應用就有多廣。 不難想像將 DBC 放到另一個星球上。 地球上的科學家可以將 數位指示發送到那台 DBC, 製造新的藥物 或製造合成有機物體, 來產生氧氣、食物、 燃料,或建造出材料, 用這種方式,讓該星球 更適合人類居住。
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With digital information traveling at the speed of light, it would only take minutes to send those digital instructions from Earth to Mars, but it would take months to physically deliver those same samples on a spacecraft. But for now, I would be satisfied beaming new medicines across the globe, fully automated and on demand, saving lives from emerging infectious diseases and printing personalized cancer medicines for those who don't have time to wait.
如果用光速來傳送數位資訊, 只要花幾分鐘, 就能把數位指示從地球 發送到火星, 但如果要用太空船 來實際遞送同樣的樣本, 會花數個月。 但目前,我已經很滿足,我們 可以向全球各地發送新的藥品, 過程完全自動化,有求必應, 拯救人命,對抗新興的感染性疾病, 並為沒有時間等待的人, 列印出個人化的癌症藥物。
Thank you.
謝謝。
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(掌聲)