We're here today to announce the first synthetic cell, a cell made by starting with the digital code in the computer, building the chromosome from four bottles of chemicals, assembling that chromosome in yeast, transplanting it into a recipient bacterial cell and transforming that cell into a new bacterial species. So this is the first self-replicating species that we've had on the planet whose parent is a computer. It also is the first species to have its own website encoded in its genetic code. But we'll talk more about the watermarks in a minute.
今天我们在此宣布, 第一个人造细胞的诞生。 这个细胞的诞生 开始于计算机上的数字代码 建造染色体 利用了四瓶化学药剂 将那些染色体集中在酵母菌中 将其转化成为一个 受体细菌细胞 然后将这个细胞转化成 一个新的细菌物种。 所以这是在地球上,我们所知的 母体是一台计算机的 第一个实现自我复制的物种。 同时,它也是第一个 拥有通过自己的遗传密码 所编码的网站的物种。 一会儿我们将更多地 讨论水印。
This is a project that had its inception 15 years ago when our team then -- we called the institute TIGR -- was involved in sequencing the first two genomes in history. We did Haemophilus influenzae and then the smallest genome of a self-replicating organism, that of Mycoplasma genitalium. And as soon as we had these two sequences we thought, if this is supposed to be the smallest genome of a self-replicating species, could there be even a smaller genome? Could we understand the basis of cellular life at the genetic level? It's been a 15-year quest just to get to the starting point now to be able to answer those questions, because it's very difficult to eliminate multiple genes from a cell. You can only do them one at a time. We decided early on that we had to take a synthetic route, even though nobody had been there before, to see if we could synthesize a bacterial chromosome so we could actually vary the gene content to understand the essential genes for life. That started our 15-year quest to get here.
这个计划最初起源于 15年前 那时我们的团队 叫做 TIGR 研究所 我们参加了历史上最早的 对成对染色体的测序。 我们对Haemophilus流行感冒病毒做实验 然后是自我复制组织的最小的染色体, 这些染色体来自生殖支原体 一旦 我们得到了这些成对的序列, 我们想到,这是否是自我复制物种中 最小的染色体, 是否还有更小的染色体? 我们是否能够在基因层次上 理解细胞生物的根本? 经过15年的探索 现在才达到了问题的出发点 才有可能回答那些问题 因为要将多个基因从细胞中去除 是非常困难的 你一次只能去除一个 早先我们决定 我们必须采取人工合成的手段 尽管之前没有人达到这个领域 看看我们是否能够人造 一个细菌的染色体 所以事实上我们能够分辨基因的内容 去了解那些对于生命来说最基本的基因。 这样,我们就开始了15年的探索 得到了现在的成果。
But before we did the first experiments, we actually asked Art Caplan's team at the University of Pennsylvania to undertake a review of what the risks, the challenges, the ethics around creating new species in the laboratory were because it hadn't been done before. They spent about two years reviewing that independently and published their results in Science in 1999. Ham and I took two years off as a side project to sequence the human genome, but as soon as that was done we got back to the task at hand.
在我们做第一次实验之前 事实上我们邀请了 宾夕法尼亚大学的Art Caplan的团队 来做一个评估 对于在实验室创造一个新物种的 风险,挑战, 以及道德问题 因为在这之前没有人这样做过 他们花了大约两年 独立的评估 在1999年在Science杂志上发表了他们的结果。 Ham和我中断了两年的工作 去完成一个人类基因组测序工程的一个分支项目 当我们完成那个工作之后 我们又立刻回到了这个计划之中。
In 2002, we started a new institute, the Institute for Biological Energy Alternatives, where we set out two goals: One, to understand the impact of our technology on the environment, and how to understand the environment better, and two, to start down this process of making synthetic life to understand basic life. In 2003, we published our first success. So Ham Smith and Clyde Hutchison developed some new methods for making error-free DNA at a small level. Our first task was a 5,000-letter code bacteriophage, a virus that attacks only E. coli. So that was the phage phi X 174, which was chosen for historical reasons. It was the first DNA phage, DNA virus, DNA genome that was actually sequenced. So once we realized that we could make 5,000-base pair viral-sized pieces, we thought, we at least have the means then to try and make serially lots of these pieces to be able to eventually assemble them together to make this mega base chromosome. So, substantially larger than we even thought we would go initially.
2002年,我们创立了 一个新的研究所 一个生物替代能源的研究所 我们为此设立了两个目标 第一,研究 我们的科技对环境造成的冲击 以及如何更好地了解我们环境 第二,开始这项 制造人造生命的计划 去理解生命的本源。 在2003年 我们发表了我们最初的成果 Ham Smith 和 Clyde Hutchison 开发了一些新的方法 在小尺度上 制造没有错误代码的DNA 我们的第一个任务是 一个含有5000个密码子的抗菌素代码 一种专门攻击大肠杆菌的病毒 这就是 φX174 噬菌体 由于历史原因我们选择了它。 它是第一个DNA噬菌体 DNA病毒,DNA染色体 这些都已经经过了测序 当我们意识到 我们能够制造5000对长度 病毒尺寸的片段 我们认为,我们至少有这样的方法 然后尝试制造一系列连续的片段 最终将其连接在一起 来制造这个百万对长度的染色体。 实质上要比 我们开始认为所能达到的长度要长
There were several steps to this. There were two sides: We had to solve the chemistry for making large DNA molecules, and we had to solve the biological side of how, if we had this new chemical entity, how would we boot it up, activate it in a recipient cell. We had two teams working in parallel: one team on the chemistry, and the other on trying to be able to transplant entire chromosomes to get new cells. When we started this out, we thought the synthesis would be the biggest problem, which is why we chose the smallest genome.
需要很多步骤我们才能达到这一步。这有两方面的问题 首先我们需要解决制造 大DNA分子中的化学问题 另外我们还需解决生物学方面的问题 那就是如果我们有了这些新的化学成分 我们如何启动它,激活它 在受体细胞中 我们有两个小组同时进行工作 一个小组是化学方面的 另一个小组尝试 移植 整个染色体 到新的细胞 当我们开始工作时,我们认为合成是最大的问题 这就是为什么我们选择了最小的染色体
And some of you have noticed that we switched from the smallest genome to a much larger one. And we can walk through the reasons for that, but basically the small cell took on the order of one to two months to get results from, whereas the larger, faster-growing cell takes only two days. So there's only so many cycles we could go through in a year at six weeks per cycle. And you should know that basically 99, probably 99 percent plus of our experiments failed. So this was a debugging, problem-solving scenario from the beginning because there was no recipe of how to get there.
可能你们当中的一些人已经发现我们放弃了最小的染色体 转而把目标放在了更大的染色体上 我们需要解释一下这样做的原因 基本上,小的细胞 需要 一到两个月的时间才能得到结果 然后体积更大的,生长更迅速的细胞 只需要两天 所以一年之内我们只能获得很少的几个周期 对于六周为一个周期来说 你需要知道,基本上 百分之99,甚至更多的 实验都失败了 所以这更像是在调试 从最初的阶段开始解决问题 因为我们没有任何可以参照的方法 关于如何达到目标
So, one of the most important publications we had was in 2007. Carole Lartigue led the effort to actually transplant a bacterial chromosome from one bacteria to another. I think philosophically, that was one of the most important papers that we've ever done because it showed how dynamic life was. And we knew, once that worked, that we actually had a chance if we could make the synthetic chromosomes to do the same with those. We didn't know that it was going to take us several years more to get there.
我们所发表的最重要的工作之一 是在2007年 由Carole Lartigue所领导的 移植一个细菌的染色体 从一个细菌体内到另一个 我想,从哲学角度上来说,那是我们所完成的 最为重要的论文之一 因为它展示了生命是如此有活力。 我们知道,一旦这起作用了 我们就事实上有了一个机会 如果我们能够制造人造染色体 对其进行同样的移植 我们最初还不知道这将花费我们 数年的时间去完成
In 2008, we reported the complete synthesis of the Mycoplasma genitalium genome, a little over 500,000 letters of genetic code, but we have not yet succeeded in booting up that chromosome. We think in part, because of its slow growth and, in part, cells have all kinds of unique defense mechanisms to keep these events from happening. It turned out the cell that we were trying to transplant into had a nuclease, an enzyme that chews up DNA on its surface, and was happy to eat the synthetic DNA that we gave it and never got transplantations. But at the time, that was the largest molecule of a defined structure that had been made.
在2008年 我们公布了完整的人工合成 类菌质体生殖基因组 略多于五十万对的密码子 但是我没还没有成功的启动这个染色体 我们认为其中一部分的原因是它生长太慢 另外一部分 是由于细胞有各种各样的独特防御机制 来阻止这类事件的发生。 最终证明,作为移植目标的细胞 有一种核酸酶,一种在DNA表面消化它的酶 而且非常开心的吃着 我们给它的合成DNA 所以从来没有移植成功 在当时,那是最大的 有确定结构的分子 人类所制造的。
And so both sides were progressing, but part of the synthesis had to be accomplished or was able to be accomplished using yeast, putting the fragments in yeast and yeast would assemble these for us. It's an amazing step forward, but we had a problem because now we had the bacterial chromosomes growing in yeast. So in addition to doing the transplant, we had to find out how to get a bacterial chromosome out of the eukaryotic yeast into a form where we could transplant it into a recipient cell.
所以两个方面都有了进展, 但是部分的合成工作 必须完成或者能够完成, 通过使用酵母,将碎片放入酵母菌内 酵母菌将为我们标记这些碎片 这是一个让人惊喜的进步 但是我们还有一个问题,因为现在我们 将细菌染色体在酵母体内培养 所以除了进行移植之外 我们还需要解决如何的问题是如何将细菌染色体 从酵母菌内取出 以便我们能够将其移植 到受体细胞内
So our team developed new techniques for actually growing, cloning entire bacterial chromosomes in yeast. So we took the same mycoides genome that Carole had initially transplanted, and we grew that in yeast as an artificial chromosome. And we thought this would be a great test bed for learning how to get chromosomes out of yeast and transplant them. When we did these experiments, though, we could get the chromosome out of yeast but it wouldn't transplant and boot up a cell. That little issue took the team two years to solve.
于是我们的团队开发出了一种新的技术 来培养和克隆 整个细菌染色体,在酵母菌内 所以我们采用了与 Carole最初移植的相同的基因 我们在酵母菌内培养它 把它当作为一个人造的染色体 我们认为这将是一个非常棒的实验基 来学习如何将染色体从酵母菌中取出 然后移植它们 当我们进行这些实验的时候,尽管 我们能够将染色体从酵母菌内取出 但我们不能移植它去启动一个细胞。 这个小问题花了研究小组两年的时间来解决。
It turns out, the DNA in the bacterial cell was actually methylated, and the methylation protects it from the restriction enzyme, from digesting the DNA. So what we found is if we took the chromosome out of yeast and methylated it, we could then transplant it. Further advances came when the team removed the restriction enzyme genes from the recipient capricolum cell. And once we had done that, now we can take naked DNA out of yeast and transplant it.
最终发现,细菌细胞内的DNA 事实上是甲基化的 甲基化阻止限制性酶对细胞起作用, 消化DNA。 我们发现,如果我们将染色体 从酵母菌内取出并且将其甲基化 我们就能移植它了 我们又取得了更大的进步 当研究小组将限制性酶的基因移除 从受体细胞内 一旦我们完成了这些,我们就能 将裸露的DNA从酵母菌内取出并且移植它
So last fall when we published the results of that work in Science, we all became overconfident and were sure we were only a few weeks away from being able to now boot up a chromosome out of yeast. Because of the problems with Mycoplasma genitalium and its slow growth about a year and a half ago, we decided to synthesize the much larger chromosome, the mycoides chromosome, knowing that we had the biology worked out on that for transplantation. And Dan led the team for the synthesis of this over one-million-base pair chromosome. But it turned out it wasn't going to be as simple in the end, and it set us back three months because we had one error out of over a million base pairs in that sequence.
所以,今年秋天 当我们在“科学”杂志上发表我们的成果时 我们都变得过于自信了 确定我们只有 几个星期 就能最终成功启动 从酵母菌内取出的染色体 因为 类菌质体生殖问题以及它过慢的生长 大约在一年半以前 我们决定合成 更大的染色体,mycoides染色体 我们在生物学方面对 这样的移植做了足够的准备 Dan领导的小组着手合成 针对超过一百万对长度的染色体 最终证明这不是件简单的工作 它将我们的工作又倒回到了三个月 因为我们除了各小错误 在这个超过一百万对的密码子的序列中
So the team developed new debugging software, where we could test each synthetic fragment to see if it would grow in a background of wild type DNA. And we found that 10 out of the 11 100,000-base pair pieces we synthesized were completely accurate and compatible with a life-forming sequence. We narrowed it down to one fragment; we sequenced it and found just one base pair had been deleted in an essential gene. So accuracy is essential. There's parts of the genome where it cannot tolerate even a single error, and then there's parts of the genome where we can put in large blocks of DNA, as we did with the watermarks, and it can tolerate all kinds of errors. So it took about three months to find that error and repair it. And then early one morning, at 6 a.m. we got a text from Dan saying that, now, the first blue colonies existed.
所以研究小组开发了新的调试软件 通过它我们可以测试每一个合成碎片 来看看它是否能在 混乱的DNA环境中生长 我们发现 我们合成的十万对长度的片段中有十一分之十的片断 都完全的准确 相比于 生命自然形成的序列 我们把范围缩小到一个碎片 然后对其测序 发现仅仅只有一对密码子被删除 在一段重要的基因中。 这样的精确度是非常有意义的 基因的一些部分 不能忍受任何一个错误 然后也有一些部分 我们能够放入大片段的DNA障碍 如同我们对标记所做的一样 它能承受各种错误 所以我们花了三个月找到那个错误 然后修复它 之后的某天早晨六点 我收到了Dan的信息 告诉我第一个蓝色殖民地诞生了
So, it's been a long route to get here: 15 years from the beginning. We felt one of the tenets of this field was to make absolutely certain we could distinguish synthetic DNA from natural DNA. Early on, when you're working in a new area of science, you have to think about all the pitfalls and things that could lead you to believe that you had done something when you hadn't, and, even worse, leading others to believe it. So, we thought the worst problem would be a single molecule contamination of the native chromosome, leading us to believe that we actually had created a synthetic cell, when it would have been just a contaminant.
取得这个成果是一个漫长的过程 从开始到现在15年 我们感觉到 这个领域的一条原则是 必须十分的确定 我们能够区分开人造DNA 和自然DNA 早先,当你在一个全新的科学领域展开工作时 你必须考虑到所有的陷阱 以及可能误导你 在没有获得成果时认为自己取得了成果, 甚至更糟,让别人也这样认为的事例。 所以我们认为最糟糕的问题是 原本染色体的 单分子污染物 让我们相信我已经 制造了一个合成细胞 然而它只是一个污染物。
So early on, we developed the notion of putting in watermarks in the DNA to absolutely make clear that the DNA was synthetic. And the first chromosome we built in 2008 -- the 500,000-base pair one -- we simply assigned the names of the authors of the chromosome into the genetic code, but it was using just amino acid single letter translations, which leaves out certain letters of the alphabet. So the team actually developed a new code within the code within the code. So it's a new code for interpreting and writing messages in DNA. Now, mathematicians have been hiding and writing messages in the genetic code for a long time, but it's clear they were mathematicians and not biologists because, if you write long messages with the code that the mathematicians developed, it would more than likely lead to new proteins being synthesized with unknown functions.
于是,我们改进了我们的想法 关于在DNA内放置标记 来确定 DNA是否为合成的。 在2008年,我们制造了第一个 染色体 包含五十万对密码子 我们只是简单的将 制造着的名字 写进了基因密码 但是它被当作了氨基酸 单密码子的翻译 略去了字母表中固定的几个字母 所以研究小组开发了新的密码 包含了密码当中的密码 这是一套新的密码 来翻译和写入DNA中的信息 如今,数学家已经在基因密码内隐藏和写入信息 的领域研究了很长时间 但是他们只是数学家而不是生物学家 因为你写入长的信息 利用数学家开发的密码 它更有可能产生 一个新的蛋白 和未知属性。
So the code that Mike Montague and the team developed actually puts frequent stop codons, so it's a different alphabet but allows us to use the entire English alphabet with punctuation and numbers. So, there are four major watermarks all over 1,000 base pairs of genetic code. The first one actually contains within it this code for interpreting the rest of the genetic code. So in the remaining information, in the watermarks, contain the names of, I think it's 46 different authors and key contributors to getting the project to this stage. And we also built in a website address so that if somebody decodes the code within the code within the code, they can send an email to that address. So it's clearly distinguishable from any other species, having 46 names in it, its own web address. And we added three quotations, because with the first genome we were criticized for not trying to say something more profound than just signing the work.
Mike Montague和他的研究小组开发的密码 事实上放入了很多停止符号 这是一个不同的字母表 能够让我们使用 完整的英文字母表 以及符号和数字 有四个主要的标记 在所有一千对基因密码中 第一个实际上包含了它 用来翻译 剩下基因密码的密码 所以在剩下的信息中 在标记中 包含了 46个作者 以及做出关键贡献 把这个项目推动到今天的成果的人的名字 我们还写入了一个 网站的地址 如果有人解码了这些 包含在密码本身之内的密码 他们就能发送电子邮件到那个地址 这与其他物种 有明显的区别 包含46个名字在其中 以及它自己的网站地址 我们还加入了三句引言 因为在制造第一个基因时 我们因为没有表达什么有含义的东西而遭到批评 只是简单的记录了工作
So we won't give the rest of the code, but we will give the three quotations. The first is, "To live, to err, to fall, to triumph and to recreate life out of life." It's a James Joyce quote. The second quotation is, "See things not as they are, but as they might be." It's a quote from the "American Prometheus" book on Robert Oppenheimer. And the last one is a Richard Feynman quote: "What I cannot build, I cannot understand." So, because this is as much a philosophical advance as a technical advance in science, we tried to deal with both the philosophical and the technical side.
我们不会给出剩下的密码 但是我们给出这三句引言 第一条是 “活着就要犯错, 有失败也有成功, 从生命中创造出生命" 这是James Joyce所说的 第二条是“看待事物,不要看他们是什么 而要看他们可能成为什么“ 这是一句源自《美国普罗米修斯》中的话 奥本海默的自传 最后一句是Richard Feynman的话 ”我所不能制造的东西 我都不能理解“ 因为这在科学上是一个技术的进步 同样也是一个哲学的进步 我们尝试解决哲学 与技术两方面的问题
The last thing I want to say before turning it over to questions is that the extensive work that we've done -- asking for ethical review, pushing the envelope on that side as well as the technical side -- this has been broadly discussed in the scientific community, in the policy community and at the highest levels of the federal government. Even with this announcement, as we did in 2003 -- that work was funded by the Department of Energy, so the work was reviewed at the level of the White House, trying to decide whether to classify the work or publish it. And they came down on the side of open publication, which is the right approach -- we've briefed the White House, we've briefed members of Congress, we've tried to take and push the policy issues in parallel with the scientific advances.
我想在开始提问之前说的最后一件事 是我们所做的 广泛的工作 征求伦理上的审核 将问题推向了 伦理方面而不仅仅是技术的层面 这在科学界得到了广泛的讨论 在政治界 以及在联邦政府的最高层也都有讨论 甚至关于这个声明 我们在2003年所做的 这项工作是由能源部提供经费的 所以这项工作要经过 白宫的审核 来决定如何将这项工作归类和公布 最终他们决定公开发布 这是正确的途径 我们对白宫做了简报 对国会做了简报 我们尝试推动 政治上政策 与科学上的进步同步
So with that, I would like to open it first to the floor for questions. Yes, in the back.
那么,我 下面接受提问。 在后面的那位
Reporter: Could you explain, in layman's terms, how significant a breakthrough this is please?
记者:你能用通俗的语言解释一下 这个突破到底有多大的意义
Craig Venter: Can we explain how significant this is? I'm not sure we're the ones that should be explaining how significant it is. It's significant to us. Perhaps it's a giant philosophical change in how we view life. We actually view it as a baby step in terms of, it's taken us 15 years to be able to do the experiment we wanted to do 15 years ago on understanding life at its basic level. But we actually believe this is going to be a very powerful set of tools and we're already starting in numerous avenues to use this tool.
Craig Venter: 需要我们解释它的意义? 我不确定我们能够解释它有多么重大的意义 它对我们来说是很有意义的 也许这是一个重大的哲学观念转变 关于我们如何看待生命这个问题上 我们实际上认为这还只是第一步 我们花了15年才成功的 做了我们15年前想要做 的实验 来理解生命最基本的层次 但是我们相信 这将成为一套非常强大的工具 而且我们已经开始 在各个方面 利用这个工具
We have, at the Institute, ongoing funding now from NIH in a program with Novartis to try and use these new synthetic DNA tools to perhaps make the flu vaccine that you might get next year. Because instead of taking weeks to months to make these, Dan's team can now make these in less than 24 hours. So when you see how long it took to get an H1N1 vaccine out, we think we can shorten that process quite substantially. In the vaccine area, Synthetic Genomics and the Institute are forming a new vaccine company because we think these tools can affect vaccines to diseases that haven't been possible to date, things where the viruses rapidly evolve, such with rhinovirus. Wouldn't it be nice to have something that actually blocked common colds? Or, more importantly, HIV, where the virus evolves so quickly the vaccines that are made today can't keep up with those evolutionary changes.
我们在研究所 现在有国立卫生研究所 在与Novartis一同进行一个项目 尝试使用这些新的 合成DNA工具 可能制造流感疫苗 明年你们就或许就能见到了。 因为相比于之前花费数周甚至数月来制造这些 Dan的研究小组现在能够在 24小时之内制造出来 所以当你们在看制造H1N1疫苗需要多长时间时 我么想我们可以缩短这个过程 这是相当有实际价值的 在疫苗领域 合成基因公司以及研究所 将成立一个新的疫苗公司 因为我们认为这个工具将对疫苗很有作用 对于那些现在来说不可能治愈的疾病 那些病毒快速进化的疾病 比如鼻病毒 如果有药物将防治普通感冒会不会是件很好的事情? 或者更重要的,艾滋病毒 这种病毒进化得如此之快 今天制造的疫苗 都赶不上 它们进化的速度
Also, at Synthetic Genomics, we've been working on major environmental issues. I think this latest oil spill in the Gulf is a reminder. We can't see CO2 -- we depend on scientific measurements for it and we see the beginning results of having too much of it -- but we can see pre-CO2 now floating on the waters and contaminating the beaches in the Gulf. We need some alternatives for oil. We have a program with Exxon Mobile to try and develop new strains of algae that can efficiently capture carbon dioxide from the atmosphere or from concentrated sources, make new hydrocarbons that can go into their refineries to make normal gasoline and diesel fuel out of CO2.
同样,在合成基因公司 我们一直在 环境问题上开展工作 我认为最近的墨西哥湾漏油 是一个警醒。 我们看不到二氧化碳 我们依靠对其科学的测量 看到初步的结果 二氧化碳过量了。 但是我们现在能看到二氧化碳的前身 漂浮在水面上 污染着墨西哥湾的海岸 我们需要一些东西来 代替石油 我们与艾森克美孚公司有一项合作计划 尝试开发新的海藻品种 能够有效地吸收二氧化碳 从大气和浓缩原料中 制造新的碳氢化合物输送进入他们的精炼厂 制造汽油 不制造二氧化碳的柴油机燃料
Those are just a couple of the approaches and directions that we're taking.
这只是我们考虑到的一些 方面和途径
(Applause)
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