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.
我来给大家讲讲制造合成细胞 和打印生命。 首先,给你们讲个简短的故事。 2013年3月31号, 我和团队收到了一封来自 国际卫生组织的电邮, 提醒我们说,有两个中国人 在感染H7N9禽流感不久后死亡了。 随着病毒开始迅速在中国传播, 人们担心病毒会在全球扩散。 尽管有生产流感疫苗 和阻止病毒传播的方法, 但至少也要需要花上 6个月的时间。 因为只能选择一种60年前发明的, 过时且缓慢的流感疫苗生产方法。
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.
病毒需要从受感染的患者中分离出来, 打包然后运送到严密的设施中, 在那儿,科学家将病毒注入鸡蛋, 孵化上几个星期, 从而为接下来需要 多个步骤,耗时数月的 疫苗生产过程做好准备。 我和团队之所以收到这个邮件 是因为我们刚刚发明出 一台生物打印机, 这台打印机可以即时从互联网上 下载流感疫苗指令并打印出来。 这极大加快了疫苗的生产过程, 具有拯救成千上万人生命的潜力。
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.
生物打印机利用了 我们读写DNA的能力, 并让我们开始把目光聚焦在 我们称之为生物传送的技术上面。 我是个用DNA来造东西的 生物学家和工程师。 不管你们信不信,我的爱好之一是 把DNA打散,再组合起来, 以便更好地理解它的工作原理。 我可以编辑和编程DNA去做事情, 就如同码农编程计算机一样。 但我们的应用程序不一样。 它们创造生命。 如自我复制的活细胞, 以及疫苗和疗法之类的东西, 这在过去是根本不可能的。
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.
这是国家科学奖章获得者 克雷格 · 文特尔(Craig Venter) 和诺贝尔奖得主 哈姆 · 史密斯(Ham Smith)。 这两位有着相似的远见, 即,所有生物体的功能和特征, 包括病毒和活细胞, 都被写入了DNA的代码中, 如果可以读写DNA的代码, 那么他们就可以 在千里之遥进行重建。 这就是我们所说的生物传送。 为了证明这一观点, 克雷格和哈姆树立了一个目标, 在历史上首次, 从计算机的DNA代码开始, 去制造合成细胞。 我意思是,得了, 一个想养家糊口的科学家, 做做尖端研究,这就够好了。
(Laughter)
(笑声)
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.
基因组是一个 生物体完整的DNA集合。 继2003年国际社会共同协作, 以识别人类完整 基因蓝图为目标的 人类基因组计划后, 基因组学的革命发生了。 科学家们开始掌握读取DNA的技术。 这项技术的目的,是确定有机体中 所有的A,C,T和G碱基的 排列顺序。 但我做的事情大不相同。 我需要掌握书写DNA的技巧。 就像图书的作者, 一开始写个短句, 或DNA序列, 但很快就变成书写段落, 然后是完整的DNA代码小说, 去为蛋白质和活细胞 做出重要的生物指示。 活细胞是自然界制造新产品的 最高效机器, 占药品生产总市场的25%, 价值几十亿美金。
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.
我们知道,一旦细胞 可以像电脑一样编程, 书写DNA会推动 生物经济进一步发展。 我们也清楚,书写DNA 可以增强生物传送… 从DNA代码开始, 打印已定义的生物材料。 为了实现这些愿景, 我的团队第一次 从电脑上的DNA代码中 创造了一种合成细菌细胞。 合成DNA是一种商品。 你可以从一些公司 订购到非常短的DNA片段, 他们采用的方法是 从构成DNA的G, A, T 和 C 这四瓶化学物质开始, 为你合成非常短的DNA片段。
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."
在过去15年左右, 我的团队开发了 一种把DNA短片段拼接在一起, 形成完整细菌基因组的技术。 我们创造的最大基因组 包含100多万字母。 是普通小说平均长度的两倍多, 我们必须把每一个字母 都按正确顺序排列, 不能有丝毫差错。 我们开发了一个流程 来完成这个任务, 我称之为 “一步体外等温重组法”。
(Laughter)
(笑声)
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.
但是,意外的是,科学界并不喜欢 这个技术上准确的名字, 并决定把它命名为“吉布森组装法”。 吉布森组装法现在是黄金标准工具, 被全球各地的实验室应用于 制造或短或长的DNA片段。
(Applause)
(鼓掌)
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.
一旦我们用化学方法 合成了完整的细菌基因组, 我们的下个挑战,就是找到 把它转变成能独立生存、 自我复制的细胞的方法。 我们的解决方法是把基因组 看作细胞的操作系统, 而细胞内则含有 启动基因组所需的硬件。 在经历无数的尝试和失败后, 我们开发了一种 可以重新编程细胞的程序, 通过将某个细胞的基因组 替换成另一个细胞的基因组, 它甚至可以将某种细菌 转化为另一种细菌。 这种基因移植技术为科学家, 而非自然母亲编写基因组 铺平了道路。 2010年,当所有这些 我们开发来读写DNA的技术都已就绪, 我们就联合宣告了 第一个合成细胞的诞生。 理所当然,我们将其 命名为“辛西娅”。
(Laughter)
(笑声)
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.
自从1995年第一个 细菌基因组被测序以来, 已经有成千上万的完整 细菌基因组被测序和储存在 电脑数据库中。 合成细胞的诞生证明了 我们可以逆转这个过程的概念: 从计算机中取出一个 完整的细菌基因组序列, 并将这些信息转换成一种 带有其所构建物种所有预期特征的 能独立生存,自我复制的细胞。
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.
现在我可以理解 为什么那么多人会有 对这种基因操纵水平的 安全性的担忧。 尽管这项技术有可能 带来巨大的社会效益, 它也有可能造成伤害。 考虑到这一点, 早在进行第一次实验之前, 我们的团队就开始 与公众和政府合作, 寻找解决方案, 负责任地开发和管理这项新技术。 这些讨论的成果之一, 是对每个客户 和客户的DNA合成订单进行筛选, 确保病原体或毒素 不会被坏人利用, 或被科学家意外制造出来。 所有可疑的订单都会报告给FBI 和其他相关执法机构。
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.
合成细胞技术将为 下一次工业革命提供动力, 以应对全球可持续性挑战的方式, 去改变行业和经济。 其应用潜力是无穷无尽的。 你可以想象 可再生生物材料做成的衣服, 工程微生物生产的生物燃料汽车, 生物可降解聚合物制成的塑料, 以及在病人床边 就可以打印的定制疗法。 创造合成细胞的大量努力 使我们成为书写DNA的全球领导者。 在这一过程中,我们 发现了书写DNA更快, 更精确和更可靠的方式。
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.
因为这些技术的稳健性, 我们发现可以很容易地 将过程自动化, 将实验室的工作流程 从科学家的手中 转移到机器上面。 2013年,我们创造了 第一台DNA打印机。 我们把它命名为BioXP。 它的DNA书写功能在我的团队和 全球研究者的 各种应用场景中, 有着绝对重要的地位。
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BioXp诞生之后不久, 我们就收到了中国H7N9 禽流感恐慌的电子邮件。 当时,中国的科学家团队 已经分离出了病毒, 测序了DNA结构,并将 序列上传到了互联网。 在美国政府的要求下, 我们下载了DNA序列, 不到12个小时内, 就在BioXp上打印了出来。 我们在诺华的合作者 迅速将合成DNA转化为流感疫苗。 与此同时,使用的技术可追溯到 20世纪40年代的疾病防控中心, 还在等待来自中国的病毒样本, 这样他们才可以开始 以鸡蛋为基础的方法。 首次,我们提前开发了 针对这种具备新的 潜在危险的毒株的流感疫苗, 而美国政府从我们 这里订购了一批药物。
(Applause)
(鼓掌)
This was when I began to appreciate, more than ever, the power of biological teleportation.
于是,我开始 比任何时候都更为欣赏 生物远距离传送力量。
(Laughter)
(笑声)
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.
自然的,心里有了这个底, 我们就着手制造生物传送器。 我们称之为DBC。 这是数字生物转换器的缩写。 与预制短链DNA 开始的BioXp不同的是, DBC从数字化DNA代码开始, 将DNA代码转化为生物实体, 比如DNA,RNA,蛋白质,甚至病毒。 你可以把BioXp想象成DVD播放器, 需要插入DVD光盘, 而DBC则相当于Netflix (在线播放平台)。 为了制造DBC, 我团队的科学家跟软件 和仪器仪表工程师合作, 将多项实验室的工作流程 整合到一个盒子里面。 其中包括用软件算法来 预测要构建的DNA, 用化学方法将碱基结构单元 构成的DNA片段连接成短链, 用吉布森组装法将这些短链 拼接成更长的片段, 以及用生物学方法 将DNA转化为像蛋白质 那样的其他生物实体。
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.
这是产品的原型。 虽然它不完美,但却非常有效。 它能够制造治疗药物和疫苗。 以前在实验室工作流程中 需要耗时数周或数月的工作, 如今在1-2天内就能完成。 而且它无需任何人工干预, 电子邮件即可激活, 这个电子邮件可以来自 全球任何地方。 我们喜欢把DBC比喻成传真机。 传真机接收图像和文件, 而DBC接收生物材料。 想想传真机是如何演化的。 1840年代的原型 与今天的传真机相比, 简直无法辨认。 上世纪80年代,很多人 仍然不知道传真机是什么, 即便知道了, 他们也很难理解 在世界另一端即刻复制图像的概念。 而今天,传真机做的所有事情 都被植入到了我们的智能手机中, 当然,我们早已把数字信息的 快速交换视为理所当然。
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.
这是今天我们的DBC的样子。 我们想象DBC以类似于 传真机的方式发展。 我们正在努力减少仪器尺寸, 努力让基础技术 更可靠,更廉价,更快,更准确。 在合成DNA时,准确性是极其重要的, 因为一个DNA字母的改变 就可能影响一种药物是否有效, 这个合成细胞是存活还是死亡。
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.
DBC对于从DNA开始的 药物的分布式制造是很有用的。 世界上每所医院都可以使用DBC 在病人床边打印个性化药物。 我甚至想象着, 有一天可以实现人手一台DBC, 连上家中的电脑或智能手机, 就可以去下载他们的处方, 例如胰岛素或抗体疗法。 在世界各地的战区, DBC也将会派上用场, 它可以快速应对疾病的爆发。 例如,乔治亚州亚特兰大的 疾病防控中心, 可以将流感疫苗的指令 发送到世界另一端的DBC, 这样流感疫苗就可以在前线生产。 这种流感疫苗甚至可以专门针对 在当地流行的流感病毒。 将疫苗通过数字文件发送, 而不再将其打包运出, 可以拯救成千上万的生命。
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.
当然,梦想有多大, 舞台就有多大。 不难想象,在另一个星球上 放置这么一台DBC。 地球上的科学家就可以 将数字指令发送到DBC, 去制造新药物,或合成生物, 以产生氧气,食物, 燃料或建筑材料, 这不失为一种把外星球 变成适合人类居住的方法。
(Applause)
(鼓掌)
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.
数字信息以光速前进, 数字指令从地球传到火星 只需要几分钟。 但如果通过太空船去 运送这些实体样本 则需要耗时数月。 但就目前而言,能在全球范围内, 完全自动化和根据需求 打印出新药物, 挽救感染了新发传染病的生命, 为那些没有时间等待的人打印个性化的 癌症药物,就已经让我感到很满足了。
Thank you.
谢谢。
(Applause)
(鼓掌)