※ [本文转录自 nfsong 信箱] 作者: vintw (阳光好青年) 看板: Gossiping 标题: Re: [爆卦] 人造细菌,创造出新的生命!! 时间: Fri May 21 08:26:35 2010 看了一下论文和报导， 距离原PO所说的"只利用基本化学物质材料, 合成打造出一种细菌"还有一段距离， 如果用游戏主机来比喻：(当然不是很严谨的比喻，请生物专家们多多包涵) 现在的基因工程大多像是改机， 也就是主机板上面加一颗晶片或接线绕过一颗晶片，然後看看结果如何等等。 而这个实验办到的是： 某人买了所有PS3上面的晶片和空板後，把它合体塞到XBOX360的盒子里面开机可以玩。 但是最後成品的内部架构几乎都和PS3一样(只差一点点)，盒子和电源等也是XBOX360的。 这件事当然和自己从塑胶粒和晶圆作出完整的游戏主机(从0创造生命)，还有一点距离。 就连随意的在主机上加上自己想要的功能这个目标目前也还未达成。 所以我们离人体练成或是新人类等等还有很长一段距离要走。 但是这个实验依然是很重要的里程碑。 类似的研究与争议在几年前就有出现过了，在这篇报导中也有提到， JCVI本是生科领域顶尖的研究机构之一， Craig Venter已经有好多篇Nature / Science / PLoS等顶级期刊论文 作者里面的Hamilton O. Smith是1978年的诺贝尔生医奖得主，阵容坚强。 八卦是：John Craig Venter 虽然是学术成就极高的一名大师， 但是他总试着把科学上面的发现私有化然後拿来卖钱，包含他发现的基因也去请专利， 这样的作法，造成了搞不好哪天你体内的某个基因却被某家公司拿去申请专利的隐忧， 关於生命科学上的发现是不是可以申请专利然後拿来营利，将会是未来法律的挑战之一。 下面试着翻译一下Science的新闻稿，大家或许可以参考一下会更了解， 我的英文不好，生物也不是专门，有翻译错误的地方还请各位不吝指正。 合成基因组为细菌带来新生命 Synthetic Genome Brings New Life to Bacterium 伊莉莎白‧潘妮西 Elizabeth Pennisi 十五年来，克莱格·凡特都再追寻一个梦想：由蓝图建立一个基因组，进而创造出合成的 生命。今天，他和他的JCVI(以他命名的实验室)实验室团队，在马里兰州的洛克威尔以 及加州的圣地亚哥，宣布他们已经实现了这个梦想。在本周的Science Express期刊中， 他们介绍了制造细菌染色体的详细步骤，并且将染色体成功的转殖到细菌中取代了原本 的DNA。透过合成的基因组，微生物细胞开始自我复制并且制造新的蛋白质。 For 15 years, J. Craig Venter has chased a dream: to build a genome from scratch and use it to make synthetic life. Now, he and his team at the J. Craig Venter Institute (JCVI) in Rockville, Maryland, and San Diego, California, say they have realized that dream. In this week's Science Express (www.sciencemag.org/cgi/content/abstract/science.1190719), they describe the stepwise creation of a bacterial chromosome and the successful transfer of it into a bacterium, where it replaced the native DNA. Powered by the synthetic genome, that microbial cell began replicating and making a new set of protein 马克‧培德，来自奥勒冈州波特兰的理德学院的哲学家兼人工生命科学期刊的编辑表示； 这是"生物学和生物技术历史上决定性的一刻"。来自马里兰州巴尔的摩约翰霍普金斯医 学院的酵母菌生物学家杰夫‧博克表示："这为合成基因组技术领域开创了一个重要的里 程碑"。 This is "a defining moment in the history of biology and biotechnology," says Mark Bedau, a philosopher at Reed College in Portland, Oregon, and editor of the scientific journal Artificial Life. "It represents an important technical milestone in the new field of synthetic genomics," says yeast biologist Jef Boeke of Johns Hopkins University School of Medicine in Baltimore, Maryland. 凡特团队所合成的基因组几乎和天然细菌所具备的一样。这项成就奠基於庞大的经费： 估计约四千万美金，以及许多人的努力：20位研究员努力了超过十年。但是，尽管这项 实验成功了，想要人工设计出可以制造石油或是具有医药用途的基因组，并且把这些基 因组丢到细菌里面"开机"却还是一件不实际的事。保罗‧凯姆，来自夫拉格斯塔的北亚历 桑纳大学的分子基因学家表示："在基因工程师可以可以混合、配对、以及完全设计生物 的基因组之前，我们还有极大的挑战"。 The synthetic genome created by Venter's team is almost identical to that of a natural bacterium. It was achieved at great expense, an estimated $40 million, and effort, 20 people working for more than a decade. Despite this success, creating heavily customized genomes, such as ones that make fuels or pharmaceuticals, and getting them to "boot" up the same way in a cell is not yet a reality. "There are great challenges ahead before genetic engineers can mix, match, and fully design an organism's genome from scratch," notes Paul Keim, a molecular geneticist at Northern Arizona University in Flagstaff. 本周公开的"合成"细菌起源於凡特和他在JCVI实验室的同事克莱德‧哈奇森三世以及 汉米尔顿‧史密斯的一个计画：他们希望找出维持细菌生命的最短基因组，同时加入人 工基因，让细菌得以变成制造人类所需元素的工厂。在1995年，由三人所领导的团队成 功的定序了一种叫做Mycoplasma genitalium细菌的的染色体，染色体的总长度为 六十万，是已知非共生生物里面最短的。这个微生物体内大约有500个基因，研究发现 删掉其中的100个基因并不会造成负面影响。 The "synthetic" bacteria unveiled this week have their origins in a project headed by Venter and JCVI colleagues Clyde Hutchison III and Hamilton Smith to determine the minimal instructions needed for microbial life and from there add genes that could turn a bacterium into a factory producing compounds useful for humankind. In 1995, a team led by the trio sequenced the 600,000-base chromosome of a bacterium called Mycoplasma genitalium, the smallest genome of a free-living organism. The microbe has about 500 genes, and researchers found they could delete 100 individual genes without ill effect (Science, 14 February 2003, p. 1006). 但是要证明上述实验提出的基因组是生存的最小所需，却需要合成整条细菌的染色体， 并且让它可以在受体细胞内正常运作，这两个步骤却因为操纵整条染色体的技术并不存 在而延宕了好几年。在2007年，凡特、史密斯、哈奇森和他们的同事们终於成功的将一种 细菌的染色体转殖到另一种细菌上。2008年，他们成功的合成出带有特殊"浮水印"DNA的 M. genitalium染色体，这些浮水印可以帮助区分人工和自然的染色体。 But confirming the minimal genome suggested by those experiments required synthesizing a full bacterial chromosome and getting it to work in a recipient cell, two steps that have taken years because the technology to make and manipulate whole chromosomes did not exist. In 2007, Venter, Smith, Hutchison, and colleagues finally demonstrated that they could transplant natural chromosomes from one microbial species to another (Science, 3 August 2007, p. 632). By 2008, they showed that they could make an artificial chromosome that matched M. genitalium's but also contained "watermark" DNA sequences that would enable them to tell the synthetic genome from the natural one (Science, 29 February 2008, p. 1215). 但是把这两个步骤合在一起却陷入了僵局。一部分原因是M. genitalium这个细菌长的 实在太慢，导致一个实验要花好几个礼拜。所以研究团队决定中途更换细菌，开始定序 基因组长度为一百万但是却长的比较快的M. mycoides，并且开始合成它的染色体。去年 ，他们成功的把M. mycoides的染色体取出来，修改过後转殖回一种近亲细菌 M.capricolum里面。所以下一步就是证明：整条合成的细菌DNA也可以如法炮制。 But combining those steps became bogged down, in part because M. genitalium grows so slowly that one experiment can take weeks to complete. The team decided to change microbes in midstream, sequencing the 1-million-base genome of the faster-growing M. mycoides and beginning to build a synthetic copy of its chromosome. Last year, they showed they could extract the M. mycoides natural chromosome, place it into yeast, modify the bacterial genome, and then transfer it to M. capricolum, a close microbial relative (Science, 21 August 2009, p. 928; 25 September 2009, p. 1693). The next step was to show that the synthetic copy of the bacterial DNA could be handled the same way. 研究人员从采购DNA序列作为建造他们的合成染色体的第一步。他们向一家公司买了超过 一千条长度为1080的序列，这些序列包含了M. mycoides的全基因组。 为了把这些序列结合起来，每条序列的尾巴80个硷基都和下一段序列重叠。为了让重组 过的基因可以被辨识，研究人员在其中的四段DNA序列中藏入了编码过的电子信箱， 许多参与计画人员的姓名，和几句名言。 The researchers started building their synthetic chromosome by going DNA shopping. They bought from a company more than 1000 1080-base sequences that covered the whole M. mycoides genome; to facilitate their assembly in the correct order, the ends of each sequence had 80 bases that overlapped with its neighbors. So that the assembled genome would be recognizable as synthetic, four of the ordered DNA sequences contained strings of bases that, in code, spell out an e-mail address, the names of many of the people involved in the project, and a few famous quotations. 透过酵母菌一步步的结合整条合成DNA，研究人员先成功了长度为一万的序列， 接着是十万，最後是完整的基因组(一百万)。但是，当他们开始把合成的基因阻塞进 M. capricolum细菌中时，什麽事都没发生。接下来就跟程式设计师帮软体除错一样， 他们有系统的尝试转殖各种自然与人工DNA的组合。等到他们终於锁定了合成DNA中仅仅 一个字的错误时，已经过了三个月的时间。 Using yeast to assemble the synthetic DNA in stages, the researchers first stitched together 10,000-base sequences, then 100,000-base sequences, and finally the complete genome. However, when they initially put the synthetic genome into M. capricolum, nothing happened. Like computer programmers debugging faulty software, they systematically transplanted combinations of synthetic and natural DNA, finally homing in on a single-base mistake in the synthetic genome. The error delayed the project 3 months. 经过好几个月的转殖各种失败组合，研究团队的运气终於在上个月变好。 生物学家发现蓝色的菌落在周末快速的於培养皿中成长(蓝色表示这些细胞是新的人工基因 组)。计画负责人丹尼尔‧吉勃森马上传讯给凡特报喜。"我拿了我的摄影机冲进去拍 (培养皿)"凡特说到。 After months of unsuccessfully transplanting these various genome combinations, the team's fortune changed about a month ago when the biologists found a blue colony of bacteria had rapidly grown on a lab plate over the weekend. (Blue showed the cells were using the new genome). Project leader Daniel Gibson sent Venter a text message declaring success. "I took my video camera in and filmed [the plate]," says Venter. 他们把这个菌落的DNA定序，确认这些细菌具有合成的DNA，并且确认这些细菌的确是制造 M. mycoides而不是M capricolum的蛋白质。这个菌落就像是一般的M. mycoides一样成长 。凡特说："显然我们把一种细胞变成了另外一种"。 They sequenced the DNA in this colony, confirming that the bacteria had the synthetic genome, and checked that the microbes were indeed making proteins characteristic of M. mycoides rather than M capricolum. The colony grew like a typical M. mycoides as well. "We clearly transformed one cell into another," says Venter. 田纳西州纳许维尔的范德比尔特大学的分子生物学家安东尼‧佛斯特表示："这是个很令 人兴奋的成就"。但是他和其他学者仍然强调这项研究并没有制造出真正合成的生命， 因为基因是被放在一个既存的细胞中。 "That's a pretty amazing accomplishment," says Anthony Forster, a molecular biologist at Vanderbilt University in Nashville, Tennessee. Still, he and others emphasize that this work didn't create a truly synthetic life form, because the genome was put into an existing cell. 研究人员强调，由凡特团队所开发的技术目前还无法吸引任何潜在的生物恐怖份子。 不过，来自加州柏克莱大学、研究合成生物学的人类学家保罗‧拉比诺表示："这项实验 的确改变了道德上的想像"。"长远看来，这技术将被大量的用在合成人工基因。"麻省理 工学院的社会科学家的肯尼斯‧欧表示："目前，我们对未来可能带来的利益和风险可说 是一无所知。" At the moment, the techniques employed by Venter's team are too difficult to appeal to any potential bioterrorists, researchers stress. Nonetheless, "this experiment will certainly reconfigure the ethical imagination," says Paul Rabinow, an anthropologist at the University of California, Berkeley, who studies synthetic biology. "Over the long term, the approach will be used to synthesize increasingly novel designed genomes," says Kenneth Oye, a social scientist at the Massachusetts Institute of Technology in Cambridge. "Right now, we are shooting in the dark as to what the long-term benefits and long-term risks will be." 欧补充说道：随着越来越多"人工的"生命出现，主管机关应该尽速制定相关的规范。 来自纽约州立大学石溪分校，在2002年带领团队成功制造出第一个合成病毒的 爱卡德‧威默表示："很不幸的是，(该技术)还是有被滥用的机会" As ever more "artificial" life comes into reach, regulatory agencies will need to establish the proper regulations in a timely fashion, adds Oye. "The possibility of misuse unfortunately exists," says Eckard Wimmer of Stony Brook University in New York state, who led a team that in 2002 created the first synthetic virus (Science, 9 August 2002, p. 1016). 凡特表示JCVI已经申请了涵盖该项成果的数个专利，这些专利最後将归於为此计划提供 大部分经费的他的公司：Synthetic Genomics所有。渥太华的技术监督组织ETC Group 认为这样的举动将导致合成生命的垄断，但是其他人并不担心。欧表示：基於目前的状 况，取得并持有这些专利，"Synthetic Genomics不可能成为合成生物学界的微软"。 Venter says that JCVI has applied for several patents covering the work, assigning them to his company, Synthetic Genomics, which provided much of the funding for the project. A technology watchdog group, ETC Group in Ottawa, has argued that these actions could result in a monopoly on synthesized life (Science, 15 June 2007, p. 1557), but others are not worried. Given the current climate for granting and upholding patents of this type, says Oye, "it is unlikely that Synthetic Genomics will become the Microsoft of synthetic biology." "可以肯定的是"，博克说："有趣的生物将会从凡特的实验室中一个个冒出来"。 "One thing is sure," Boeke says. "Interesting creatures will be bubbling out of the Venter Institute's labs." -- Sincerely. --VinTW --

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